Chapter 8
Miscellaneous conditions and substances
Suicide attempts and suicidal gestures are frequently encountered in psychiatric and general practice, and psychotropic drugs are often taken in overdose. This section gives brief details of the toxicity in overdose of commonly used psychotropics (Table 8.1). It is intended to help guide drug choice in those thought to be at risk of suicide and to help identify symptoms of overdose. This section gives no information on the treatment of psychotropic overdose and readers are directed to specialist poisons units. In all cases of suspected overdose, urgent referral to acute medical facilities is, of course, strongly advised.
Table 8.1 Psychotropic drugs in overdose
Drug or drug group |
Toxicity in overdose |
Smallest dose likely to cause death |
Signs and symptoms of overdose |
Antidepressants |
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Agomelatine1 |
Probably low |
No deaths reported. In early trials, 800 mg was maximum tolerated dose |
Sedation |
Bupropion2-5 |
Moderate |
Around 4.5 g |
Tachycardia, seizures, QRS prolongation, QT prolongation, arrhythmia |
Duloxetine6-8 |
Low |
Unclear - no deaths from single overdose reported |
Drowsiness, bradycardia, hypotension. May be asymptomatic |
Lofepramine9-11 |
Low |
Unclear. Fatality unlikely if lofepramine taken alone |
Sedation, coma, tachycardia, hypotension |
MAOIs (not moclobemide)9,12-14 |
High |
Phenelzine - 400 mg Tranylcypromine - 200 mg |
Tremor, weakness, confusion, sweating, tachycardia, hypertension |
Mianserin15-17 |
Low |
Unclear but probably more than 1 g. Fatality unlikely if mianserin taken alone |
Sedation, coma, hypotension, hypertension, tachycardia, possible QT prolongation |
Mirtazapine2,18-21 |
Low |
Unclear but probably more than 2.25 g. Fatality unlikely in overdose of mirtazapine alone |
Sedation; even large overdose may be asymptomatic. Tachycardia/hypertension sometimes seen |
Moclobemide22-23 |
Low |
Unclear, but probably more than 8 g. Fatality unlikely if moclobemide taken alone |
Vomiting, sedation, disorientation |
Reboxetine2,24 |
Low |
Not known. Fatality unlikely in overdose of reboxetine alone |
Sweating, tachycardia, changes in blood pressure |
SSRIs10,11,25-27 |
Low |
Unclear. Probably above 1-2 g. Fatality unlikely if SSRI taken alone |
Vomiting, tremor, drowsiness, tachycardia, ST depression. Seizures and QT prolongation possible. Citalopram most toxic of SSRIs in overdose (coma, seizures, arrhythmia); escitalopram is less toxic28,29 |
Trazodone7,30-33 |
Low |
Unclear but probably more than 10 g. Fatality unlikely in overdose of trazodone alone |
Drowsiness, nausea, hypotension, dizziness. Rarely QT prolongation-arrhythmia |
TCAS9,12,13,34,35 (not lofepramine) |
High |
Around 500 mg. Doses over 50 mg/kg usually fatal |
Sedation, coma, tachycardia, arrhythmia (QRS, QT prolongation), hypotension, seizures |
Venlafaxine2,36-41 (assume same for desvenlafaxine) |
Moderate |
Probably above 5 g, but seizures may occur after ingestion of 1 g |
Vomiting, sedation, tachycardia, hypertension, seizures. Rarely QT prolongation, arrhythmia, rhabdomyolysis. Very rarely cardiac arrest/MI, heart failure |
Vortioxetine42 |
Low |
Unclear |
Nausea, somnolence, diarrhoea, pruritis |
Antipsychotics |
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Amisulpride43,43-45 |
Moderate |
Around 16 g |
QT prolongation, arrhythmia, cardiac arrest |
Aripiprazole46-49 |
Low |
Unclear. Fatality unlikely when taken alone |
Sedation, lethargy, gastrointestinal disturbance, drooling |
Asenapine50 |
Probably low |
Unclear. No deaths from overdose reported |
Sedation, confusion, facial dystonia, benign ECG changes |
Butyrophenones51-53 |
Moderate |
Haloperidol - probably above 500 mg. Arrhythmia may occur at 300 mg |
Sedation, coma, dystonia, NMS, QT prolongation, arrhythmia |
Clozapine54,55 |
Moderate |
Around 2 g, much less in non-tolerant individuals |
Lethargy, coma, tachycardia, hypotension, hypersalivation, pneumonia, seizures |
Iloperidone56,57 |
Probably moderate |
Unclear but probably more than 500 mg |
Potent effect on QT interval. Sedation, tachycardia, hypotension likely |
Lurasidone58 |
Probably low |
Unclear |
Very limited information. Minimal effect on QT interval |
Olanzapine54,59-61 |
Moderate |
Unclear. Probably substantially more than 200 mg |
Lethargy, confusion, myoclonus, myopathy, hypotension, tachycardia, delirium. Possibly QT prolongation |
Phenothiazines51,62-64 |
Moderate |
Chlorpromazine 5-10 g |
Sedation, coma, tachycardia, arrhythmia, pulmonary oedema, hypotension, QT prolongation, seizures, dystonia, NMS |
Quetiapine54,65-70 |
Low |
Unclear. Probably more than 5 g. Fatalities rare |
Lethargy, delirium, tachycardia, QT prolongation, respiratory depression, hypotension, rhabdomyolysis, NMS |
Risperidone54,71,72 (assume same for paliperidone) |
Low |
Unclear. Fatality rare in those taking risperidone alone |
Lethargy, dystonia, tachycardia, changes in blood pressure, QT prolongation. Renal failure with paliperidone |
Ziprasidone73-78 |
Low |
Around 10 g. Fatality unlikely when taken alone |
Drowsiness, lethargy. QT prolongation, Torsades |
Mood stabilisers |
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Carbamazepine79,80 |
Moderate |
Around 20 g, but seizures may occur at around 5 g |
Somnolence, coma, respiratory depression, ataxia, seizures, tachycardia, arrhythmia, electrolyte disturbance |
Lamotrigine81-83 |
Low |
Unclear. No deaths from overdose reported |
Drowsiness, vomiting, ataxia, tachycardia, dyskinesia |
Lithium84-87 |
Low (acute overdose) |
Acute overdose does not normally result in fatality. Insidious, chronic toxicity is more dangerous |
Nausea, diarrhoea, tremor, confusion, weakness, lethargy, seizures, coma, cardiovascular collapse, bradycardia, arrhythmia, heart block |
Valproate88-92 |
Moderate |
Unclear but probably more than 20 g. Doses over 400 mg/kg cause severe toxicity |
Somnolence, coma, cerebral oedema, respiratory depression, blood dyscrasia, hypotension, hypothermia, seizures, electrolyte disturbance (hyper ammonaemia) |
Others |
|||
Benzodiazepines93,94 |
Low |
Probably more than 100 mg diazepam equivalents. Fatality unusual if taken alone. Alprazolam is most toxic |
Drowsiness, ataxia, nystagmus, respiratory dysarthria, depression, coma |
Methadone95,96 |
High |
20-50 mg may be fatal in non-users. Co-ingestion of benzodiazepines increases toxicity |
Drowsiness, nausea, hypotension, respiratory depression, coma, rhabdomyolysis |
Modafinil97,98 |
Low |
Unclear. Overdoses of > 6 g have not caused death |
Tachycardia, insomnia, agitation, anxiety, nausea, hypertension, dystonia |
Zolpidem99,100 |
Low |
Unclear. Probably > 200 mg. Fatality rare in those taking zolpidem alone |
Drowsiness, agitation, respiratory depression, tachycardia, coma |
Zopiclone93,101,102 |
Low |
Unclear. Probably > 100 mg. Fatality rare in those taking zopiclone alone |
Ataxia, nausea, diplopia, drowsiness, coma |
ECG, electrocardiogram; MAOI, monoamine oxidase inhibitor; MI, myocardial infarction; NMS, neuroleptic malignant syndrome; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.
High= Less than 1 week's supply likely to cause serious toxicity or death Moderate= 1–4 weeks' supply likely to cause serious toxicity or death Low= Death or serious toxicity unlikely even if more than 1 month's supply taken |
Almost all psychotropics currently used in clinical practice have haematology or biochemistry-related adverse effects that may be detected using routine blood tests. While many of these changes are idiosyncratic and not clinically significant, others, such as the agranulocytosis associated with agents such as clozapine, will require regular monitoring of the full blood count. In general, where an agent has a high incidence of biochemical/haematological side-effects or a rare but potentially fatal effect, regular monitoring is required as discussed in other sections.
For other agents, laboratory-related side-effects are comparatively rare (prevalence usually less than 1%), are often reversible upon cessation of the putative offending agent and not always clinically significant although expert advice should be sought. It should further be noted that medical co-morbidity, polypharmacy and the effects of non-prescribed agents, including substances of abuse and alcohol, may also influence biochemical and haematological parameters. In some cases, where a clear temporal association between starting the agent and the onset of laboratory changes is unclear, then withdrawal and re-challenge with the agent in question may be considered. Where there is doubt as to the aetiology and significance of the effect, the appropriate source of expert advice should always be consulted.
Tables 8.2 and 8.3 summarise those agents with identified biochemical and haematological effects, with information compiled from various sources.1–11 In many cases the evidence for these various effects is limited, with information obtained mostly from case reports, case series and information supplied by manufacturers. For further details about each individual agent, the reader is encouraged to consult the appropriate section of the Guidelines as well as other, specialist sources, particularly product literature relating to individual drugs.
Table 8.2 Summary of biochemical changes associated with psychotropic drugs
Parameter |
Reference range |
Agents reported to raise levels |
Agents reported to lower levels |
Alanine transferase |
0-45IU/L (may be higher in males and obese subjects) |
Antipsychotics: asenapine, benperidol, chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine Antidepressants: agomelatine, duloxetine, mianserin, mirtazapine, moclobemide, monoamine oxidase inhibitors, SSRIs (especially paroxetine and sertraline); TCAs, trazodone, venlafaxine Anxiolytics/hypnotics: barbiturates, benzodiazepines, chloral hydrate, chlormethiazole, promethazine Miscellaneous agents: caffeine, dexamfetamine, disulfiram, opioids Mood stabilisers: carbamazepine, lamotrigine, valproate |
Vigabatrin |
Albumin |
3.5-4.8 g/dL (gradually decreases after age 40) |
Microalbuminuria may be a feature of metabolic syndrome secondary to psychotropic use (especially phenothiazines, clozapine, olanzapine and possibly quetiapine) |
Chronic use of amfetamine or cocaine |
Alkaline phosphatase |
50-120 IU/L |
Caffeine (excess/chronic use), carbamazepine, clozapine, disulfiram, duloxetine, galantamine, haloperidol, memantine, modafinil, nortriptyline, olanzapine, phenytoin, sertraline; also associated agents that induce neuroleptic malignant syndrome |
None known |
Amylase |
< 300 IU/L |
Clozapine, donepezil, methadone, olanzapine, opiates, pregabalin, rivastigmine, SSRIs (rarely), valproate |
None known |
Aspartate aminotransferase |
10-50 IU/L (values slightly higher in males) |
As for alanine transferase |
Trifluoperazine |
Bicarbonate |
22-30 mmol/L |
None known |
Agents associated with SIADH: all antidepressants, antipsychotics (clozapine, haloperidol, olanzapine, phenothiazines, pimozide, risperidone/paliperidone, quetiapine), carbamazepine |
Bilirubin |
3-20 pmol/L (total bilirubin) |
Amitriptyline, benzodiazepines, carbamazepine, chlordiazepoxide, chlorpromazine, clomethiazole, disulfiram, imipramine, fluphenazine, meprobamate, phenothiazines, phenytoin, promethazine, trifluoperazine, valproate |
None known |
C-reactive protein |
< 10 μg/mL |
Buprenorphine (rare) |
None known |
Calcium (corrected) |
2.2-2.6 mmol/L |
Lithium (rare) |
Barbiturates, haloperidol |
Carbohydrate-deficient transferrin |
1.9-3.4 g/L |
None known |
None known |
Chloride |
98-107 mmol/L |
None known |
Medications associated with SIADH: all antidepressants, antipsychotics (clozapine, haloperidol, olanzapine, phenothiazines, pimozide, risperidone/paliperidone, quetiapine), carbamazepine |
Cholesterol (total) |
< 5.2 mmol/L |
Antipsychotic treatment, especially those implicated in the metabolic syndrome (phenothiazines, clozapine, olanzapine and quetiapine). Rarely: aripiprazole, beta-blockers, disulfiram, memantine, mirtazapine, modafinil, phenytoin, rivastigmine, and venlafaxine |
Ziprasidone |
Creatine Kinase |
< 90 IU/L |
Clozapine (when associated with seizures), donepezil, olanzapine; also associated with agents causing neuroleptic malignant syndrome and SIADH; cocaine, dexamfetamine |
None known |
Creatinine |
60-110 pmol/L |
Clozapine, lithium,lurasidone, thioridazine, valproate, medications associated with rhabdomyolysis (benzodiazepines, dexamfetamine, pregabalin, thioridazine); may also be also associated with agents causing neuroleptic malignant syndrome and SIADH |
None known |
Ferritin |
Males: 40-340μg/L; Females: 14-150 μg/L |
None known |
None known |
Gamma-glutamyl transferase |
< 60 IU/L (higher levels may be found in males) |
Antidepressants: mirtazapine, SSRIs (paroxetine and sertraline implicated); TCAs, trazodone, venlafaxine Anticonvulsants/mood stabilisers: carbamazepine, lamotrigine, phenytoin, phenobarbitone, valproate Antipsychotics: benperidol, chlorpromazine, clozapine, fluphenazine, haloperidol, olanzapine, quetiapine, Miscellaneous: barbiturates, clomethiazole, dexamfetamine, modafinil |
None known |
Glucose |
Fasting: 2.8-6.0 mmol/L Random: < 11.1 mmol/L |
Antidepressants: MAOI*, SSRI, TCAs* Antipsychotics: chlorpromazine, clozapine, olanzapine*, quetiapine, and others Substances of abuse: methadone, opioids Other: beta-blockers*, bupropion, donepezil, galantamine, lithium All antipsychotics associated with hyperglycaemia (excluding amisulpride, lurasidone, aripiprazole and ziprasidone), glantamine, methadone, morphine, TCAs |
Rarely with duloxetine, haloperidol, pregabalin, TCAs Medications associated with metabolic syndrome may result in raised or decreased glucose levels |
Glycated haemoglobin |
3.5-5.5% (4-6% in diabetics) |
As above |
Lithium, MAOIs, SSRIs |
Lactate dehydrogenase |
90-200 U/L (levels rise gradually with age) |
TCAs (especially Imipramine), valproate, methadone, agents associated with neuroleptic malignant syndrome |
None known |
Lipoproteins: HDL |
> 1.2 mmol/L |
Carbamazepine, phenobarbitone, phenytoin |
Olanzapine, phenothiazines, valproate |
Lipoproteins: LDL |
< 3.5 mmol/L |
Beta-blockers, caffeine (controversial), chlorpromazine, clozapine, memantine, mirtazapine, modafinil, olanzapine, phenothiazines, quetiapine, risperidone/paliperidone, rivastigmine, venlafaxine |
None known |
Phosphate |
0.8-1.4 mmol/L |
Acamprosate, carbamazepine, dexamfetamine, agents associated with neuroleptic malignant syndrome |
None known |
Potassium |
3.5-5.0 mmol/L |
Pregabalin |
Haloperidol, lithium, mianserin, reboxetine, rivastigmine, alcohol, caffeine, cocaine |
Prolactin |
Normal < 350 mU/L; Abnormal > 600 mU/L; |
Antidepressants: especially MAOIs and TCAs, venlafaxine also implicated Antipsychotics: amisulpride, haloperidol, pimozide, risperidone/paliperidone, sulpiride (aripiprazole, asenapine, clozapine, lurasidone, olanzapine, quetiapine and ziprasidone have minimal effects on prolactin levels) |
None known |
Protein (total) |
60-80 g/L |
None known |
None known |
Sodium |
135-145 mmol/L |
None known |
Benzodiazepines, carbamazepine, chlorpromazine, donepezil, duloxetine, haloperidol, lithium, memantine, mianserin, phenothiazines, reboxetine, rivastigmine, SSRIs (especially fluoxetine), tricyclic antidepressants (especially amitriptyline) Hyponatraemia should be considered in any patient on an antidepressant who develops confusion, convulsions or drowsiness |
Thyroid-stimulating hormone |
0.3-4.0 mU/L |
Aripiprazole, carbamazepine, lithium, rivastigmine |
Moclobemide |
Thyroxine |
Free: 9-26 pmol/L; Total: 60-150 nmol/L |
Dexamfetamine, moclobemide (rare) |
Lithium (causes decreased T4 secretion), heroin, methadone (increase serum thyroxine-binding globulin), carbamazepine, phenytoin treatment. Rarely implicated: aripiprazole, quetiapine and rivastigmine |
Triglycerides |
0.4-1.8 mmol/L |
Beta-blockers, chlorpromazine, clozapine, memantine, mirtazapine, modafinil, olanzapine, quetiapine, phenothiazines, rivastigmine, valproate, venlafaxine, |
Ziprasidone (controversial) |
Tri-iodothyronine |
Free 3.0-8.8 pmol/L; Total: 1.2-2.9 nmol/L |
Heroin, methadone, moclobemide |
Free T3: valproate Total T3: carbamazepine, lithium |
Urate (uric acid) |
0.1-0.4 mmol/L |
Rarely: rivastigmine |
None known |
Urea |
1.8-7.1 mmol/L (levels increase slightly after age 40) |
Rarely with agents associated with anticonvulsant hypersensitivity syndrome and rhabdomyolysis |
None known |
* may also be associated with hypoglycaemia. HDL, high-density lipoprotein; LDL, low-density lipoprotein; MAOI, monoamine oxidase inhibitor; SIADH, syndrome of inappropriate antidiuretic hormone; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant. |
Table 8.3 Summary of haematological changes associated with psychotropic drugs
Parameter |
Reference range |
Agents reported to raise levels |
Agents reported to lower levels |
Activated partial thromboplastin time |
25-39 seconds |
Bupropion*, phenothiazines (especially chlorpromazine) |
Modafinil (rare) |
Basophils |
0.0-0.10 x 109/L |
TCAs (especially desipramine) |
None known |
Eosinophils |
0.04-0.45 x 109/L |
Amitriptyline, beta-blockers, carbamazepine, chloral hydrate, chlorpromazine, clonazepam, clozapine, donepezil, fluphenazine, haloperidol, imipramine, meprobamate, modafinil, nortriptyline, olanzapine, promethazine, quetiapine, SSRIs, tryptophan, valproate |
None known |
Erythrocytes |
Males: 4.5-6.0 x 1012/L Females: 3.8-5.2 x 1012/L |
None known |
Carbamazepine, chlordiazepoxide, chlorpromazine, donepezil, meprobamate, phenytoin, trifluoperazine |
Erythrocyte sedimentation rate |
< 20 mm/hour; Note: levels increase with age and are slightly higher in females |
Buprenorphine, clozapine, dexamfetamine, levomepromazine, maprotiline, SSRIs |
None known |
Haemoglobin |
Males: 14-18 g/dL Females: 12-16 g/dL |
None known |
Aripiprazole, barbiturates, bupropion, carbamazepine, chlordiazepoxide, chlorpromazine, donepezil, duloxetine, galantamine, MAOIs, memantine, meprobamate, mianserin, phenytoin, promethazine, rivastigmine, trifluoperazine |
Lymphocytes |
1.0-4.8 x 109/L |
Opioids, valproate |
Chloral hydrate, lithium |
Mean cell haemoglobin |
27-37 pg Note: Levels are slightly higher in males and may be raised in the elderly |
Medications associated with megaloblastic anaemia, e.g. all anticonvulsants |
None known |
Mean cell haemoglobin concentration |
300-350 g/L |
|
|
Mean cell volume |
80-100 fL |
|
|
Monocytes |
0.21-0.92 x 109/L |
Haloperidol |
None known |
Neutrophils |
2-9 x 109/L Note: may be lower in people of African descent due to benign ethnic neutropenia |
Bupropion, carbamazepine†, citalopram, chlorpromazine, clozapine†, duloxetine, fluphenazine, haloperidol, lithium, olanzapine, quetiapine, risperidone/paliperidone, rivastigmine, trazodone, venlafaxine |
Agents associated with agranulocytosis: amitriptyline, amoxapine, aripiprazole, barbiturates, carbamazepine, chlordiazepoxide, chlorpromazine, clomipramine, clozapine‡, diazepam, fluphenazine, haloperidol, imipramine, meprobamate, mianserin, mirtazapine, nortriptyline, olanzapine, promethazine, tranylcypromine, valproate |
|
|
|
Agents associated with leucopoenia: amitriptyline, amoxapine, bupropion, carbamazepine, chlorpromazine, citalopram, clomipramine, clonazepam, clozapine, duloxetine, fluphenazine, galantamine, haloperidol, lamotrigine, lorazepam, MAOIs, memantine, meprobamate, mianserin, mirtazapine, modafinil, olanzapine, oxazepam, pregabalin, promethazine, quetiapine, risperidone/paliperidone, tranylcypromine, valproate, venlafaxine Agents associated with neutropenia: trazodone, valproate |
Packed cell volume |
Adult males: 42-52% Adult females: 35-47% (levels slightly lower in pregnant versus non-pregnant women) |
None known |
None known |
Platelets |
150-400 x 109/L |
Lithium |
Amitriptyline, barbiturates, bupropion, carbamazepine, clomipramine, chlordiazepoxide, chlorpromazine, clonazepam, clozapine, diazepam, donepezil, duloxetine, fluphenazine, imipramine, lamotrigine, MAOIs, meprobamate, mirtazapine, olanzapine, promethazine, risperidone/paliperidone, rivastigmine, sertraline, tranylcypromine, trazodone, trifluoperazine, valproate, cocaine, methadone Agents associated with impaired platelet aggregation: chlordiazepoxide, citalopram, diazepam, fluoxetine, fluvoxamine, paroxetine, sertraline |
Prothrombin time/ International Normalised Ratio |
10-13 seconds |
Fluoxetine, fluvoxamine, disulfiram; bupropion, mirtazapine |
Barbiturates, carbamazepine, phenytoin |
Red cell distribution width |
11.5-14.5% |
Agents associated with anaemia: carbamazepine, chlordiazepoxide, citalopram, clonazepam, diazepam, lamotrigine, mirtazapine, sertraline, tranylcypromine, trazodone, valproate, venlafaxine |
None known |
Reticulocyte count |
0.5-1.5% |
None known |
Carbamazepine, chlordiazepoxide, chlorpromazine, meprobamate, phenytoin, trifluoperazine |
* may raise or lower levels † Rare, usually associated with leucopoenia. ‡ Note that in rare cases clozapine has been associated with a 'morning pseudo-neutropenia' with lower levels of circulating neutrophil levels. As neutrophil counts may show circadian rhythms, repeating the FBC at a later time of day may be instructive. FBC, full blood count; MAOI, monoamine oxidase inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant. |
A Product Licence (PL) is granted when regulatory authorities are satisfied that the drug in question has proven efficacy in the treatment of a specified disorder, along with an acceptable side-effect profile, relative to the severity of the disorder being treated and other available treatments. Licensed indications are preparation specific, outlined in the Summary of Product Characteristics (SPC), and may be different for branded and generic formulations of the same drug.1 In the US product 'labelling' has a similar legal status to EU licensing.
The decision of a manufacturer to seek a PL for a given indication is essentially a commercial one; potential sales are balanced against the cost of conducting the necessary clinical trials. It therefore follows that drugs may be effective outside their licensed indications for different disease states, age ranges, doses and durations. The absence of a formal PL or labelling may simply reflect the absence of controlled trials supporting the drug's efficacy in these areas. In other cases (e.g. sertraline or quetiapine in generalised anxiety disorder) there is sufficient evidence but a licence has not been sought by the manufacturer. Importantly, however, it is possible that trials have been conducted but given negative results. Clinicians often assume that drugs with a similar mode of action will be similarly effective for a given indication, and in many cases this may be true. For example, the efficacy of aripiprazole, olanzapine, quetiapine and risperidone in reducing behavioural and psychological symptoms (BPSD) in people with dementia, is similar2 yet only risperidone is licensed for this indication.
Prescribing a drug within its licence or labelling does not guarantee that the patient will come to no harm. Likewise, prescribing outside a licence does not mean that the risk–benefit ratio is automatically adverse. In the BPSD example given above, risperidone is not clearly better tolerated than other antipsychotics.2 In the UK, prescribing outside a licence, usually called 'off-label', does confer extra responsibilities on prescribers, who will be expected to be able to show that they acted in accordance with a respected body of medical opinion (the Bolam test)3 and that their action was capable of withstanding logical analysis (the Bolitho test).4
It has been suggested that off-label prescribing in psychiatry is less likely to be supported by a strong evidence base than off-label prescribing in other areas of medicine.5 In psychiatry, small (underpowered) studies (with wide confidence intervals) often influence practice, particularly with respect to treatment resistant illness. When these small studies are combined in the form of a meta-analysis, considerable heterogeneity is often found suggesting publication bias (that is, that negative studies are not published). Treatments may therefore become incorporated into 'routine custom and practice' in the absence of any evidence supporting efficacy and/or tolerability, and these treatments may sometimes continue to be used despite the findings of later, larger, and more definitive negative studies.
The psychopharmacology special interest group at the Royal College of Psychiatrists has published a consensus statement on the use of licensed medicines for unlicensed uses.6 They note that unlicensed use is common in general adult psychiatry with cross-sectional studies showing that up to 50% of patients are prescribed at least one drug outside the terms of its licence. They also note that the prevalence of this type of prescribing is likely to be higher in patients under the age of 18 or over 65, in those with a learning disability, in women who are pregnant or lactating and in those patients who are cared for in forensic psychiatry settings. The main recommendations in the consensus statement are summarised in Box 8.1.
Box 8.1 Summary of the consensus statement on the use of licensed medicines for unlicensed uses |
Before prescribing 'off-label':
The more experimental the unlicensed use is, the more important it is to adhere to the above guidance. |
Table 8.4 gives examples of common unlicensed uses of drugs in psychiatric practice. These examples would all fulfil the Bolam and Bolitho criteria in principle. An exhaustive list of unlicensed uses is impossible to prepare as:
Note that some drugs do not have a UK licence for any indication. Two commonly prescribed examples in psychiatric practice are immediate release formulations of melatonin (used to treat insomnia in children and adolescents) and pirenzepine (used to treat clozapine-induced hypersalivation). Awareness of the evidence base and documentation of potential benefits, side-effects and patient consent are especially important here.
Table 8.4 Common unlicensed uses of drugs in psychiatric practice
Drug/drug group |
Unlicensed use(s) |
Further information |
Second-generation antipsychotics |
Psychotic illness other than schizophrenia |
Licensed indications vary markedly, and in most cases are unlikely to reflect real differences in efficacy between drugs |
Clozapine |
Rapid cycling bipolar disorder |
Some evidence to support efficacy when standard treatments have failed to control symptoms |
Cyproheptadine |
Akathisia |
Some evidence to support efficacy in this distressing and difficult to treat side-effect of antipsychotics |
Fluoxetine |
Maintenance treatment of depression |
Few prescribers are likely to be aware that this is not a licensed indication in the UK |
Melatonin (Circadin) |
Insomnia in children |
Licence covers adults > 55 years only. Probably preferable to unlicensed formulations of melatonin |
Methylphenidate |
ADHD in children under 6 years |
Established clinical practice |
|
ADHD in people over 18 years |
Supported by evidence base |
Naltrexone |
Self-injurious behaviour in people with learning disabilities |
Limited evidence base. Acceptable in specialist hands |
Sodium valproate |
Treatment and prophylaxis of bipolar disorder |
Established clinical practice |
ADHD, attention deficit hyperactivity disorder. |
Frank B et al. Psychotropic medications and informed consent: a review. Ann Clin Psychiatry 2008; 20:87–95.
General Medical Council. Good practice in prescribing and managing medicines and devices. 2013. http://www.gmc-uk.org/guidance/ethical_guidance/14316.asp.
Target symptoms improve to varying degrees in approximately one-third of patients given a placebo.1,2 Adverse effects also occur; the so-called nocebo effect.2 Although pharmacologically inert, placebo can cause direct physiological effects, at least in the short term, that are consistent with the effects of active drugs. This has been demonstrated in neuroimaging studies.3,4 The exact neurobiological response varies with the target illness.2,5 In many psychiatric conditions the effect size of placebo is substantial;6 often greater than the effect size of drugs used in general medicine.7 Proving the efficacy of psychotropic drugs is thus challenging; much more challenging than in general medicine where placebo effects are often absent (e.g. type I diabetes).
The following considerations apply when interpreting the results of placebo-controlled studies. Although the references for each point are drawn from the depression literature, the same principles apply to the treatment of other disorders. The relative importance of each point will vary depending on the disorder that is being treated.
Drug interactions with alcohol are complex. Many patient-related and drug-related factors need to be considered. It can be difficult to predict accurately outcomes because a number of processes may occur simultaneously or consequently.
Alcohol (ethanol) is absorbed from the gastrointestinal tract and distributed in body water. The volume of distribution is smaller in women and the elderly where plasma levels of alcohol will be higher for a given 'dose' of alcohol than in males. Approximately 10% of ingested alcohol is subjected to first pass metabolism by alcohol dehydrogenase (ADH). A small proportion of alcohol is metabolised by ADH in the stomach. The remainder is metabolised in the liver by ADH and CYP2E1; women have less capacity to metabolise via ADH than men. CYP2E1 plays a minor role in occasional drinkers but is an important and inducible metabolic route in chronic, heavy drinkers. CYP1A2, CYP3A4 and many other CYP enzymes also play a minor role.5,6
CYP2E1 and ADH convert alcohol to acetaldehyde which is both the toxic substance responsible for the unpleasant symptoms of the 'antabuse reaction' (e.g. flushing, headache, nausea, malaise), and the compound implicated in hepatic damage. Acetaldehyde is further metabolised by aldehyde dehydrogenase to acetic acid and then to carbon dioxide and water.
All of the enzymes involved in the metabolism of alcohol exhibit genetic polymorphism. For example, 40% of people of Asian origin are poor metabolisers via ADH. Chronic consumption of alcohol induces CYP2E1 and CYP3A4. The effects of alcohol on other hepatic metabolising enzymes have been poorly studied.
The metabolism of alcohol is summarised in Figure 8.1.
Interactions are difficult to predict in alcohol misusers because two opposing processes may be at work: competition for enzymatic sites during periods of intoxication (increasing drug plasma levels) and enzyme induction prevailing during periods of sobriety (reducing plasma levels). See Tables 8.5 and 8.6. In chronic drinkers, particularly those who binge drink, serum levels of prescribed drugs may reach toxic levels during periods of intoxication with alcohol and then be sub-therapeutic when the patient is sober. This makes it very difficult to optimise treatment of physical or mental illness.
Figure 8.1 Metabolism of alcohol. *Minor route in occasional drinkers; major route in misusers and at higher blood alcohol concentration.
Interactions of uncertain aetiology include increased blood alcohol concentrations in people who take verapamil and decreased metabolism of methylphenidate in people who consume alcohol.
Table 8.5 Co-administration of alcohol and substrates for CYP2E1 and CYP3A4
|
Substrates for enzyme Note: this is not an exhaustive list |
Effects in an intoxicated patient |
Effects in a chronic, sober drinker |
CYP2E1 |
Paracetamol Isoniazid Phenobarbitone Warfarin |
Competition between alcohol and drug leading to reduced rates of metabolism of both compounds. Increased plasma levels may lead to toxicity |
Activity of CYP2E1 is increased up 10-fold. Increased metabolism of drugs potentially leading to therapeutic failure |
CYP3A4 |
Benzodiazepines Carbamazepine Clozapine Donepezil Galantamine Mirtazapine Risperidone Sildenafil Tricyclics Valproate Venlafaxine 'Z' hypnotics |
Competition between alcohol and drug leading to reduced rates of metabolism of both compounds. Increased plasma levels may lead to toxicity |
Increased rate of drug metabolism potentially leading to therapeutic failure. Enzyme induction can last for several weeks after alcohol consumption ceases. |
Table 8.6 Drugs that inhibit alcohol dehydrogenase and aldehyde dehydrogenase
Enzyme |
Inhibited by |
Potential consequences |
Alcohol dehydrogenase |
Aspirin H2 antagonists |
Reduced metabolism of alcohol resulting in higher plasma levels for longer periods of time |
Aldehyde dehydrogenase |
Chlorpropamide Disulfiram Griseofulvin Isoniazid Isosorbide dinitrate Metronidazole Nitrofurantoin Sulphamethoxazole Tolbutamide |
Reduced ability to metabolise acetaldehyde leading to 'antabuse' type reaction: facial flushing, headache, tachycardia, nausea and vomiting, arrhythmias and hypotension |
Alcohol enhances inhibitory neurotransmission at gamma-aminobutyric acid (GABA) receptors and reduces excitatory neurotransmission at glutamate N-methyl-D-aspartate (NMDA) receptors. It also increases dopamine release in the mesolimbic pathway and may have some effects on serotonin and opiate pathways. Given these actions, alcohol alone would therefore be expected to cause sedation, amnesia, ataxia and give rise to feelings of pleasure (and/or worsen psychotic symptoms in vulnerable individuals). See Table 8.7.
Alcohol can cause or worsen psychotic symptoms by increasing dopamine release in mesolimbic pathways. The effect of antipsychotic drugs may be competitively antagonised, rendering them less effective.
Electrolyte disturbances secondary to alcohol-related dehydration can be exacerbated by other drugs that cause electrolyte disturbances such as diuretics.
Note that heavy alcohol consumption can lead to hypoglycaemia in people with diabetes who take insulin or oral hypoglycaemics. Theoretically there is an increased risk of lactic acidosis in patients who take metformin with alcohol. Alcohol can also increase blood pressure.
Chronic drinkers are particularly susceptible to the gastrointestinal irritant effects of aspirin and NSAIDs.
Table 8.7 Pharmacodynamic interactions with alcohol
Effect of alcohol |
Effect exacerbated by |
Potential consequences |
Sedation |
Other sedative drugs, e.g. Antihistamines Antipsychotics Baclofen Benzodiazepines Lofexidine Opiates Tizanidine Tricyclics Z-hypnotics |
Increased CNS depression ranging from increased propensity to be involved in accidents through to respiratory depression and death |
Amnesia |
Other amnesic drugs, e.g. Barbiturates Benzodiazepines Z-hypnotics |
Increased amnesic effects ranging from mild memory loss to total amnesia |
Ataxia |
ACE inhibitors Beta-blockers Calcium channel blockers Nitrates Adrenergic a-receptor antagonists, e.g. Clozapine Risperidone Tricyclics |
Increased unsteadiness and falls |
ACE, angiotensin-converting enzyme; CNS, central nervous system. |
Table 8.8 Psychotropic drugs: choice in patients who continue to drink
|
Safest choice |
Best avoided |
Antipsychotics |
Sulpiride and amisulpride Paliperidone, if depot required Non-sedative and renally excreted |
Very sedative antipsychotics such as chlorpromazine and clozapine |
Antidepressants |
SSRI - citalopram, sertraline Potent inhibitors of CYP3A4 (fluoxetine, paroxetine) may decrease alcohol metabolism in chronic drinkers |
TCAs, because impairment of metabolism by alcohol (while intoxicated) can lead to increased plasma levels and consequent signs and symptoms of overdose (profound hypotension, seizures, arrhythmias and coma) Cardiac effects can be exacerbated by electrolyte disturbances Combinations of TCAs and alcohol profoundly impair psychomotor skills MAOIs as can cause profound hypotension. Also potential interaction with tyramine-containing drinks which can lead to hypertensive crisis |
Mood stabilisers |
Valproate Carbamazepine Note: higher plasma levels achieved during periods of alcohol intoxication may be poorly tolerated |
Lithium, because it has a narrow therapeutic index and alcohol-related dehydration and electrolyte disturbance can precipitate lithium toxicity |
MAOI, monoamine oxidase inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant. |
Note: in the presence of pharmacokinetic interactions, pharmacodynamic interactions will be more marked. For example, in a chronic heavy drinker who is sober, enzyme induction will increase the metabolism of diazepam which may lead to increased levels of anxiety (treatment failure). If the same patient becomes intoxicated with alcohol, the metabolism of diazepam will be greatly reduced as it will have to compete with alcohol for the metabolic capacity of CYP3A4. Plasma levels of alcohol and diazepam will rise (toxicity). As both alcohol and diazepam are sedative (via GABA affinity), loss of consciousness and respiratory depression may occur.
Note: be aware of the possibility of hepatic failure or reduced hepatic function in chronic alcohol misusers. See section on 'Hepatic impairment' in Chapter 7. Also note risk of hepatic toxicity with some recommended drugs (e.g. valproate). Psychotropic drugs of choice are given in Table 8.8.
Joint Formulary Committee. BNF 67 March-September 2014 (online). London: Pharmaceutical Press; 2014. http://www.medicinescomplete.com/ mc/bnf/current/
Stockley's Drug Interactions. London: Pharamceutical Press; 2014. https://www.medicinescomplete.com/
The most common method of consuming nicotine is by smoking cigarettes. One-quarter of the general population, 40–50% of those with depression1 and 70–80% of those with schizophrenia smoke.2 Nicotine causes peripheral vasoconstriction, tachycardia and increased blood pressure.3 Smokers are at increased risk of developing cardiovascular disease. People with schizophrenia who smoke are more likely to develop the metabolic syndrome, compared with those who do not smoke.4 As well as nicotine, cigarettes also contain tar (a complex mixture of organic molecules, many carcinogenic), a cause of cancers of the respiratory tract, chronic bronchitis and emphysema.5 Electronic cigarettes, it is claimed, contain only nicotine, which has very limited toxicity and is not thought to be carcinogenic. E-cigarettes are thus preferred for all smokers, albeit with some reservations in regard to quality control of content and the so-called re-normalisation of smoking.
Nicotine is highly addictive; an effect which may be at least partially genetically determined.6 People with mental illness are 2–3 times more likely than the general population to develop and maintain a nicotine addiction.1 Chronic smoking contributes to the increased morbidity and mortality from respiratory and cardiovascular disease that is seen in this patient group. Nicotine also has psychotropic effects. Smoking can affect the metabolism (and therefore the efficacy and toxicity) of drugs prescribed to treat psychiatric illness.7 See section on 'Smoking and psychotropic drugs' in this chapter. Nicotine use may be a gateway to experimenting with other psychoactive substances.
Nicotine is highly lipid-soluble and rapidly enters the brain after inhalation. Nicotine receptors are found on dopaminergic cell bodies and stimulation of these receptors leads to dopamine release.1 Dopamine release in the limbic system is associated with pleasure: dopamine is the brain's 'reward' neurotransmitter. Nicotine may be used by people with mental health problems as a form of 'self-medication' (e.g. to alleviate the negative symptoms of schizophrenia or antipsychotic-induced extrapyramidal sideeffects [EPS] or for its anxiolytic effect8). Drugs that increase the release of dopamine reduce the craving for nicotine. They may also worsen psychotic illness (see the section on 'Nicotine and smoking cessation' in Chapter 6).
Nicotine improves concentration and vigilance.1 It also enhances the effects of glutamate, acetylcholine and serotonin.8
Seventy to eighty per cent of people with schizophrenia regularly smoke cigarettes2 and this increased tendency to smoke predates the onset of psychiatric symptoms.9 Possible explanations are as follows: smoking causes dopamine release, leading to feelings of well-being and a reduction in negative symptoms;8 to alleviate some of the side-effects of antipsychotics such as drowsiness and EPS1 and cognitive slowing;10 as a means of structuring the day (a behavioural filler); a familial vulnerability11 or as a means of alleviating the deficit in auditory gaiting that is found in schizophrenia.12
Nicotine may also improve working memory and attentional deficits.13–15 Nicotinic receptor agonists may have beneficial effects on neurocognition,16,17 although none is yet licensed for this purpose. Note though that cholinergic drugs may exacerbate nicotine dependence.18 A single photon emission computed tomography (SPECT) study has shown that the greater the occupancy of striatal D2 receptors by antipsychotic drugs, the more likely the patient is to smoke.19 This may partly explain the clinical observation that smoking cessation may be more achievable when clozapine (a weak dopamine antagonist) is prescribed in place of a conventional antipsychotic. It has been suggested that people with schizophrenia find it particularly difficult to tolerate nicotine withdrawal symptoms.7 Switching to nicotine replacement therapy (NRT) or e-cigarettes may thus be a preferred option.20
In 'normal' individuals a moderate consumption of nicotine is associated with pleasure and a decrease in anxiety and feelings of anger.21 The mechanism of this anxiolytic effect is not understood. People who suffer from anxiety and/or depression are more likely to smoke22,23 and find it more difficult to stop.21,24 This is compounded by the observation that nicotine withdrawal can precipitate or exacerbate depression in those with a history of the illness,21 and cigarette smoking may directly increase the risk of symptoms of depression.25 In marked contrast, a recent analysis suggests that stopping smoking actually improves depression and anxiety.26 These contradictory findings are explained by the fact that early withdrawal worsens depression whereas successful cessation improves depression in the longer term.
Patients with depression are at increased risk of cardiovascular disease. By directly causing tachycardia and hypertension,3 nicotine may, in theory, exacerbate this problem. More importantly, smoking is a well known independent risk factor for cardiovascular disease, probably because it hastens athlerosclerosis. A Cochrane review27 suggests smoking cessation is achievable in depressed smokers.
By increasing dopaminergic neurotransmission, nicotine provides a protective effect against both drug-induced EPS and idiopathic Parkinson's disease. Smokers are less likely to suffer from antipsychotic-induced movement disorders than non-smokers1 and use anticholinergics less often.7 Parkinson's disease occurs less frequently in smokers than in non-smokers and the onset of clinical symptoms is delayed.1,28 This may reflect the inverse association between Parkinson's disease and sensation seeking behavioural traits, rather than a direct effect of nicotine.29
Polycyclic hydrocarbons in cigarette smoke are known to stimulate the hepatic microsomal enzyme system, particularly P4501A2,8 the enzyme responsible for the metabolism of many psychotropic drugs. Smoking can lower the blood levels of some drugs by up to 50%.8 This can affect both efficacy and side-effects and needs to be taken into account when making clinical decisions. The drugs most likely to be affected are: clozapine,30 fluphenazine, haloperidol, chlorpromazine, olanzapine, many tricyclic antidepressants, mirtazapine, fluvoxamine and propranolol. See section on 'Smoking and psychotropic drugs' in this chapter.
Withdrawal symptoms occur within 6–12 hours of stopping smoking and include intense craving, depressed mood, insomnia, anxiety, restlessness, irritability, difficulty in concentrating and increased appetite. Nicotine withdrawal can be confused with depression, anxiety, sleep disorders and mania. Withdrawal can also exacerbate the symptoms of schizophrenia.
See section on 'Nicotine and smoking cessation' in Chapter 6.
Aguilar MC et al. Nicotine dependence and symptoms in schizophrenia: naturalistic study of complex interactions. Br J Psychiatry 2005;186:215–21.
Ziedonis D et al. Tobacco use and cessation in psychiatric disorders: National Institute of Mental Health report. Nicotine Tob Res 2008; 10:1691–1715.
Tobacco smoke contains polycyclic aromatic hydrocarbons that induce (increase the activity of) certain hepatic enzymes (CYP1A2 in particular).1 For some drugs used in psychiatry, smoking significantly reduces drug plasma levels and higher doses are required than in non-smokers.
When people stop smoking, enzyme activity reduces over a week or so. (Nicotine replacement or use of electronic cigarettes has no effect on this process.) Plasma levels of affected drugs will then rise, sometimes substantially. Dose reduction will usually be necessary. If smoking is re-started, enzyme activity increases, plasma levels fall and dose increases are then required. The process is complicated and effects are difficult to predict. Of course, few people manage to give up smoking completely, so additional complexity is introduced by intermittent smoking and repeated attempts at stopping completely. Close monitoring of plasma levels (where useful), clinical progress and adverse effect severity are essential.
Table 8.9 gives details of psychotropic drugs known to be affected by smoking status.
Table 8.9 Psychotropic drugs affected by smoking status
Drug |
Effect of smoking |
Action to be taken on stopping smoking |
Action to be taken on re-starting |
Agomelatine2 |
Plasma levels reduced |
Monitor closely. Dose may need to be reduced |
Consider re-introducing previous smoking dose |
Benzodiazapines3,4 |
Plasma levels reduced by 0-50% (depends on drug and smoking status) |
Monitor closely. Consider reducing dose by up to 25% over one week |
Monitor closely. Consider re-starting 'normal' smoking dose |
Carbamazepine3 |
Unclear, but smoking may reduce carbamazepine plasma levels to a small extent |
Monitor for changes in severity of adverse effects |
Monitor plasma levels |
Chlorpromazine3-5 |
Plasma levels reduced. Varied estimates of exact effect |
Monitor closely. Consider dose reduction |
Monitor closely. Consider re-starting previous smoking dose |
Clozapine6-10 |
Reduces plasma levels by up to 50%. Plasma level reduction may be greater in those receiving valproate |
Take plasma level before stopping. On stopping, reduce dose gradually (over a week) until around 75% of original dose reached (i.e. reduce by 25%). Repeat plasma level one week after stopping. Anticipate further dose reductions |
Take plasma level before re-starting. Increase dose to previous smoking dose over one week. Repeat plasma level |
Duloxetine11 |
Plasma levels may be reduced by up to 50% |
Monitor closely. Dose may need to be reduced |
Consider re-introducing previous smoking dose |
Fluphenazine12 |
Reduces plasma levels by up to 50% |
On stopping, reduce dose by 25%. Monitor carefully over following 4-8 weeks. Consider further dose reductions |
On re-starting, increase dose to previous smoking dose |
Fluvoxamine13 |
Plasma levels decreased by around one-third |
Monitor closely. Dose may need to be reduced |
Dose may need to be increased to previous level |
Haloperidol14,15 |
Reduces plasma levels by around 20% |
Reduce dose by around 10%. Monitor carefully. Consider further dose reductions |
On re-starting, increase dose to previous smoking dose |
Mirtazapine16 |
Unclear, but effect probably minimal |
Monitor |
Monitor |
Olanzapine17-20 |
Reduces plasma levels by up to 50% |
Take plasma level before stopping. On stopping, reduce dose by 25%. After one week, repeat plasma level. Consider further dose reductions |
Take plasma level before restarting. Increase dose to previous smoking dose over one week. Repeat plasma level |
Tricyclic antidepressants3,4 |
Plasma levels reduced by 25-50% |
Monitor closely. Consider reducing dose by 10-25% over one week. Consider further dose reductions |
Monitor closely. Consider re-starting previous smoking dose |
Zuclopentixol21,22 |
Unclear, but effect probably minimal |
Monitor |
Monitor |
Note: Only cigarette smoking induces hepatic enzymes in the manner described abovenicotine replacement and electronic cigarettes (which do not contain polycyclic aromatic compounds) have no effect on enzyme activity. |
Caffeine is probably the most popular psychoactive substance in the world. Mean daily consumption in the UK is 350–620 mg.1 A quarter of the general population and half of those with psychiatric illness regularly consume over 500 mg caffeine/day.2 Consumption of caffeine should be routinely discussed with an individual to assess its effect on their symptoms and presentation.3 In particular, caffeine withdrawal can have a marked effect on mental and physical health. See Table 8.10 for the caffeine content of various drinks.
Chocolate also contains caffeine. Martindale lists over 600 medicines that contain caffeine.4 Most are available without prescription and are marketed as analgesics or appetite suppressants.
Table 8.10 Caffeine content of drinks
Drink |
Caffeine content |
Brewed coffee |
100 mg/cup |
Red Bull |
80 mg/can (other energy drinks may contain substantially more) |
Instant coffee |
60 mg/cup |
BlackTea |
45 mg/cup |
Green Tea |
20-30 mg/cup |
Soft drinks |
25-50 mg/can |
Table 8.11 Psychotropic effects of caffeine
Dose |
Psychotropic effect |
Generally |
CNS stimulation Increase catecholamine release, particularly dopamine7 |
Low to moderate dose |
Elation2 Peacefulness2 |
Large doses > 600 mg/day (Sensitive individuals may experience affects at lower doses) |
Anxiety8 Insomnia8 Psychomotor agitation8 Excitement8 Rambling speech8 Sometimes delirium and psychosis8 May inhibit benzodiazepine-receptor binding8 Tolerance may develop to the affects Established withdrawal syndrome exists, symptoms include: headache, depressed mood, anxiety, fatigue, irritability, nausea, dysphoria and craving9 |
The Diagnostic and Statistical Manual of Mental Disorders DSM-V16 defines caffeine intoxication as the recent consumption of caffeine, usually in excess of 250 mg accompanied by five or more of the symptoms shown in Box 8.2.
In caffeine intoxication, these symptoms cause significant distress or impairment in social, occupational or other important areas of functioning and are not due to a general medical condition or better accounted for by another mental disorder (e.g. an anxiety disorder).
Caffeine abuse or dependence as a clinical syndrome has been reported3 and Caffeine Use Disorder and Caffeine Withdrawal are both DSM-V diagnoses.
So called energy drinks contain large amounts of caffeine along with sugar, vitamins and a number of other ingredients such as guarana. There is some evidence that these drinks can improve attention and short-term memory.17 Marketing is targeted at adolescents and young adults, some of whom consume large volumes of these drinks, and seem to be particularly vulnerable to developing signs and symptoms of caffeine intoxication. Symptoms of anxiety and depression, frank suicidal behaviour and seizures have been associated with use of these products by young people.18–20
Table 8.12 Interactions of caffeine
Interacting substance |
Effect |
Comment |
CYP1A2 inhibitors: Oestrogens Cimetidine Fluvoxamine (may decrease caffeine clearance by 80%)12 Disulfiram |
Reduce caffeine clearance |
Effects of caffeine may be prolonged or increased Adverse effects may be increased May precipitate caffeine toxicity |
Cigarette smoke |
CYP1A2 inducer - increasing caffeine metabolism7 |
Smokers may require higher doses to gain desired effects7 |
Lithium |
High doses may reduce lithium levels |
Caffeine withdrawal may cause a lithium level rise13 |
MAOIs |
May enhance stimulant CNS effects |
|
Clozapine |
Caffeine may increase plasma levels by up to 60%14 |
Thought to be through competitive inhibition of CYP1A2. Other drugs affected by the enzyme include olanzapine, imipramine and clomipramine |
SSRIs |
Large doses may increase risk of serotonin syndrome15 |
|
Benzodiazepines |
Caffeine may receptor binding, acting as an antagonist |
Reduce the efficacy8 |
CNS, central nervous system; MAOI, monoamine oxidase inhibitor; SSRI, selective serotonin reuptake inhibitor. |
Box 8.2 Symptoms of caffeine intoxication |
|
In summary, caffeine:
Caffeine: In AHFS Drug Information. American Society of Health Care Pharmacists. http://www.medicinescomplete.com
Paton C, Beer D. Caffeine: the forgotten variable. Int J Psychiatry Clin Pract 2002; 5: 231–236.
Complementary therapies are those used alongside orthodox treatments with the aim of providing psychological and emotional support through the relief of symptoms. A wide range of treatments are available, most with limited or no scientific support. These therapies do not change or develop over time, there being almost no research aimed at determining best practice. Whenever an alternative treatment is shown to be active, it usually becomes part of mainstream practice.
A large proportion of the population currently use or have recently used complementary therapies (CTs).1 Most users suffer from psychiatric conditions.2,3 As health professionals are rarely consulted before purchase, a diagnosis is often not made and efficacy and side-effects are not monitored. The majority of those who use CTs are also taking conventional medicines and many people use more than one CT simultaneously.4 Many do not tell their doctor.5 The public associate natural products with safety and may be unwilling to report possible side-effects.6 Herbal medicines, in particular, can be toxic as they contain pharmacologically active substances.7 Many conventional drugs prescribed today were originally derived from plants. These include medicines as diverse as aspirin, digoxin and the vinca alkaloids used in cancer chemotherapy. Herbal medicines such as St John's wort, Ginkgo biloba, Yokukansan and Valerian are increasingly used as self-medication for psychiatric and neurodegenerative illnesses.3,8–13
Few CTs have been subject to randomised controlled trials, so efficacy is largely unproven. For some, Cochrane Reviews exist, but none support their use. These include the use of Chinese herbal medicine as an adjunct to antipsychotics in schizophrenia (promising, more evidence required)14 aromatherapy for behavioural problems in dementia (insufficient evidence, but worth further study)15,16 and hypnosis for schizophrenia (insufficient evidence, but worth further study).17 Several complementary therapies are thought to be worthy of further study in the adjunctive management of substance misuse.18 There is some preliminary, limited support for aromatherapy as an adjunct to conventional treatments in a range of psychiatric conditions.19 Folic Acid20 and Vitamin D21 have been used in depression.
There is little systematic monitoring of side-effects caused by CTs, so safety is unknown. There are an increasing number of published case reports of significant drug–herb interactions;22 these include ginkgo and aspirin or warfarin leading to increased bleeding, ginkgo and trazodone leading to coma, and ginseng and phenelzine leading to mania.23,24 The wide range of drug interactions with St John's wort are outlined in the section 'Drug interactions with antidepressants' in Chapter 4.
Some herbs are known to be very toxic.25,26 During consultation with patients or in the process of medicine reconciliation, the use of any specific complementary therapies should be explored and reviewed.
Whatever the perceived 'evidence base' for the use of complementary therapies, the feelings of autonomy engendered by (apparently) taking control of one's own illness and treatment can result in important psychological benefits irrespective of any direct therapeutic benefits of the CT; the placebo effect is likely to be important here. (see section on 'Observations on the placebo effect in mental illness' in this chapter.) There are many different complementary therapies, the most popular being homeopathy and herbal medicine with its branches of Bach's flower remedies, and Chinese and Ayurvedic medicine. Non-drug therapies such as acupuncture and osteopathy are also popular. Aromatherapy is usually considered to be a non-pharmacological treatment but this may not be the case.27 Physical exercise28 and spirituality29 have also been suggested.
Table 8.13 An introduction to complementary therapies
|
Health beliefs |
Used for |
Not suitable for |
Side-effects and other information |
Homeopathy15,17,31,32 |
|
|
|
|
Herbal medicine (phytotherapy)25,26 |
|
|
|
|
Aromatherapy16,33 |
|
|
|
|
To master one CT can sometimes take years of study. Therefore, to ensure safe and effective treatment, any referrals should be to a qualified practitioner with the Complementary and Natural Healthcare Council.30
Be aware, nonetheless, that scientific support for most complementary medicine is minimal and 'qualification' to practise may entail little in the way of examination or regulation. Moreover, much of what is taught and learned is palpable nonsense. The majority of doctors and pharmacists have no qualifications or specific training in CTs. Table 8.13 gives a brief introduction. Further reading is strongly recommended.
Rethink Mental Illness. Complementary Therapies. 2012. http://www.rethink.org/
Ernst E. Assessments of complementary and alternative medicine: the clinical guidelines from NICE. Int J Clin Pract 2010; 64:1350–1358.
Recommendations made in clinical guidelines regarding the use of medicines are based on evidence from clinical trials supplemented by clinicians' opinions of the balance between the potential benefits and potential risks of treatment. In clinical practice, however, a range of patient-related factors such as insight, health beliefs and the perceived efficacy and tolerability of treatment, influence whether medication is taken, and if so, for how long.
The patient and prescriber should agree jointly on the goals of treatment and how these can be reached. Sticking to this mutually agreed plan is termed concordance or adherence; non-adherence indicates that the treatment plan should be renegotiated, and not that the patient is at fault.
Reviews of adherence generally conclude that approximately 50% of people do not take their medication as prescribed, and that this proportion is similar across chronic physical and mental disorders.1 This, however, may be an over-simplification in that it is probable that only a very small proportion of patients are fully adherent, the majority are partially adherent to varying degrees, and a few never take any medication at all of their own volition.2
There is some variation in adherence rates both over time and across settings. For example, ten days after discharge from hospital, up to 25% of patients with schizophrenia are partially or completely non-adherent and this figure rises to 50% at one year and 75% by 2 years.3 In some mental healthcare settings the rate of non-adherence may be up to 90%.4
Poor adherence to medication is a major risk factor for poor outcomes including relapse in people with schizophrenia,5–7 bipolar disorder8 and depression.9,10 Wider health benefits are also lost. For example, compared with depressed patients who take an antidepressant, those who do not have a 20% increased risk of an incident myocardial infarction.10 As a rule of thumb, the lower the amount of prescribed medication that is taken, the poorer the outcome. There is no evidence that newer (presumed better tolerated) medicines are consistently associated with increased adherence.2
According to the World Health Organisation 'increasing the effectiveness of adherence interventions may have far greater impact on the health of the population than any improvements in specific medical treatments'; it has therefore been suggested that non-adherence should be a diagnosable condition for which active interventions are provided.11 Indeed, analyses of data collected as part of the national confidential inquiry into suicide and homicide by people with mental illness, revealed that healthcare providers that had a policy in place regarding how to manage patients who are not taking their medication as prescribed, had 20% fewer suicides than providers that did not have such a policy.12
Not surprisingly, non-adherence is known to be more common when the patient disagrees with the need for treatment, the medication regimen is complex, or the patient perceives the side-effects of treatment to be unacceptable.9 Adherence may also therefore be medication specific, where some medicines are taken regularly, others intermittently and others not at all. Notably, half of those who stop treatment don't tell their doctor. Psychiatrists generally prefer to use direct questioning over the use of more intrusive/ objective methods of assessing adherence,13 and so partial or non-adherence may go undetected.
Non-adherence can be intentional (sometimes termed 'intelligent' non-adherence) or unintentional or a mixture of both. Most non-adherence is intentional. Individual influences (which can change in any given patient over time) include the following factors.
NICE (2009)15 recommend that, as long as the patient has capacity to consent, their right not to take medication should be respected. If the prescriber considers that this decision may have an adverse effect, the reasons for the patient's decision and the prescriber's concerns should be recorded.
A number of rating scales and checklists are available that help to guide and structure discussion around attitudes to medication. The most widely used is the Drug Attitude Inventory (DAI)16 which consists of a mix of positive and negative statements about medication; 30 statements in its full form and 10 in its abbreviated form. It is designed to be completed by the patient who simply agrees or disagrees with each statement. The total score is an indicator of the patients overall perception of the balance between the benefits and harms associated with taking medication, and therefore likely adherence. Attitudes to medication as measured using the DAI have been shown to be a useful predictor of compliance over time.17 Other available checklists include the Rating of Medication Influences Scale (ROMI),18 the Beliefs about Medicines Questionnaire19 and the Medication Adherence rating Scale (MARS).7
It is very difficult to be certain about whether or not a patient is taking prescribed medicines; partial and non-adherence are almost always covert until the patient relapses. Clinicians are known to overestimate adherence rates and patients may not openly acknowledge that they are not taking all or any of their medication. NICE recommend that the patient should be asked in a non-judgemental way if they have missed any doses over a specific time period such as the previous week.15
It is also important to ask the patient about perceived effectiveness and side-effects. More intrusive methods include checks that prescriptions have been collected, asking to see the patient's medication (pill counts) and asking family or carers. For some antipsychotics such as clozapine, olanzapine and risperidone, blood tests can be useful to directly assess plasma levels. It is important to note that plasma levels of these drugs achieved with a fixed dose vary somewhat and it is not possible to accurately determine partial non-adherence (i.e. total non-adherence will be readily revealed but partial and full adherence may be difficult to tell apart). See section on 'Plasma level monitoring' in Chapter 1.
Note that few studies specifically recruit non-adherent patients (the refusal rate in such patients is likely to be high) and the specific barriers to adherence are rarely identified. The small effect size seen in many studies may simply be a consequence of this unfocused approach. Where barriers to adherence are identified and targeted interventions delivered, adherence is more likely to improve.20
NICE has reviewed the evidence for adherence over a range of health conditions.15 They conclude that no specific intervention can be recommended for all patients but, in general, adherence is maximised if:
NICE further recommend that any intervention that is used to increase adherence should be tailored to overcome the specific difficulties experienced or reported by a patient.
It is essential that the patient's perspective is understood and respected and a treatment plan agreed jointly. The following strategies may help to achieve this:
Overcoming practical difficulties can also help. Potentially useful strategies include:
The need to consider multiple strategies tailored to the needs of individual patients is also the conclusion of a Cochrane review that examined medication adherence over a wide range of medical conditions.1 Almost all of the interventions that were effective in improving adherence in long-term care were complex, and even the most effective interventions did not lead to large improvements in adherence and treatment outcomes. Haynes et al1 emphasized that there is no evidence that low adherence can be 'cured'; efforts to improve adherence must be maintained for as long as treatment is needed.
After early promise in improving insight, adherence, attitudes towards medication and rehospitalisation rates in an inpatient sample,26 further studies of Compliance therapy have failed to replicate this finding. Compliance therapy has been shown to have no advantage over non-specific counselling in either inpatients17 or outpatients,27 or those who have been clinically unstable in the last year.28
Compliance aids that contain compartments accommodating up to four doses of multiple medicines each day may be helpful in patients who are clearly motivated to take medication but find this difficult because of disorganisation or cognitive deficits. It should be noted that only 10% of non-compliant patients say that they forgot to take medication29 and that compliance aids are not a substitute for lack of insight or lack of motivation to take medication. Some medicines are unstable when removed from blister packaging and placed in a compliance aid. These include oro-dispersible formulations which are often prescribed for non-adherent patients. In addition, compliance aids are labour intensive (expensive) to fill, it can be difficult to change prescriptions at short notice and the filling of these devices is particularly error-prone.30
Meta-analyses of clinical trials have shown that the relative and absolute risks of relapse with depot maintenance treatment were 30% and 10% lower respectively, than with oral treatment31,32 when depots are used. In clinical practice, covert non-adherence is avoided; if the patient defaults from treatment, it will be immediately apparent. NICE recommends that depots are an option in patients who are known to be non-adherent to oral treatment and/or those who prefer this method of administration.33 Depots are likely to be underused, for example a recent US study found that depot preparations were prescribed for fewer than one in five patients with a recent episode of nonadherence.34 The introduction of so-called atypical depots may allow wider use of these formulations. Wider choice may lead to improved acceptability.
There is evidence from controlled trials across a number of disease areas supporting the potential of financial incentives to enhance medication adherence. Paying people to take their medication is extremely controversial, though some clinicians have found this strategy to be successful in high risk patients with psychotic illness.35 An RCT has demonstrated that modest payments improve adherence in patients with psychotic illness.36
Barnes TR. Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2011; 25:567–620.
Driving a car is important in maintaining independence and freedom. However, no one should drive if their performance is compromised. Everyone has a duty to drive reasonably and all drivers are legally responsible for accidents they cause.1
Many factors have been shown to affect driving performance. These include age, gender, personality, physical and mental state and being under the influence of alcohol, prescribed medicines, street drugs or over-the-counter medicines.2,3 Studying the effects of any of these factors in isolation is extremely difficult. Some studies have attempted to categorize medicinal drugs according to how they affect driving performance.4 Some studies have assessed the effect of medication on tests such as response-time and attention,5 but these tests do not directly measure ability or inability to drive.
It has been estimated that up to 10% of people killed or injured in road traffic accidents (RTAs) are taking psychotropic medication.5 See Table 8.14. Patients with personality disorders and alcoholism have the highest rates of motoring offences and are more likely to be involved in accidents.5 People whose driving ability may be impaired through their illness or prescribed medication should inform their insurance company. Failure to do so is considered to be 'withholding a material fact' and may render the insurance policy void.
Severe mental disorder is a prescribed disability for the purposes of the Road Traffic Act 1988.19 Regulations define mental disorder as including mental illness, arrested or incomplete development of the mind, psychopathic disorder or severe impairment of intelligence or social functioning. The licence restrictions that apply to each disorder can be found in Table 8.15. Note that licence restrictions may also apply to people with diabetes, particularly if treated with insulin or if there are established micro or macrovascular complications.
Many people with early dementia are capable of driving safely.20 All drivers with new diagnoses of Alzheimer's disease and other dementias must notify the Drivers and Vehicle Licensing Agency (DVLA).21,22 The doctor may need to make an immediate decision on safety to drive and ensure that the licensing agency is notified23 There are no data to support ongoing driving assessments as a way of maintaining driving ability or improving road safety of drivers with dementia.24
The Road Traffic Act does not differentiate between illicit drugs and prescribed medicines. In the UK, a new liability offence came into effect in the summer of 2014 for drivers who are impaired after recreational use of drugs.25 Therefore, any person who drives in a public place while unfit due to any drug, is liable to prosecution. The DVLA list of 'recreational drugs' includes some that can be prescribed such as morphine, amfetamines and benzodiazepines (the full list can be found on the MHRA website). A comprehensive report26 describing the evidence behind the new laws and legal limits for driving is available.
Table 8.14 Psychotropic drugs and driving
Drug |
Effect |
Alcohol |
Alcohol causes sedation and impaired coordination, vision, attention and informationprocessing. Alcohol-dependent drivers are twice as likely to be involved in traffic accidents and offences than licensed drivers as a whole,5 and a third of all fatal RTAs involve alcohol-dependent drivers.5 Young drivers who use alcohol in combination with illicit drugs are particularly high risk6,7 |
Anticonvulsants |
Initial, dose-related side-effects may affect driving ability (e.g. blurred vision, ataxia and sedation). There are strict rules regarding epilepsy and driving |
Antidepressants |
People who are prescribed an antidepressant have an increased risk of being involved in a RTA particularly at treatment initiation. SSRIs may have some advantages over TCAs but driving ability is still diminished compared with healthy individuals,8 suggesting that depression itself may make a major contribution9,10 Initiation effects caused by mirtazapine diminish to an extent when it is given as a single dose at night but many people experience substantial hangover. There is currently no available data on the effects of agomelatine and duloxetine on driving ability.8 |
Antipsychotics |
Sedation and EPS can impair coordination and response time.2 A high proportion of patients treated with antipsychotics may have an impaired ability to drive.11,12 One study found patients with schizophrenia taking atypical antipsychotics or clozapine performed better in tests of skills related to car-driving ability than patients with schizophrenia taking typical antipsychotics.13 Clinical assessment is required |
Hypnotics and anxiolytics |
Benzodiazepines cause sedation and impaired attention, information processing, memory and motor coordination, and along with opiates are the medicines most frequently implicated in RTAs.14 When used as anxiolytics and hypnotics, benzodiazepines, zopiclone and zolpidem are associated with an increased risk of RTAs.14 There is some gender variation in the pharmacokinetics of zolpidem with females having higher drug plasma concentrations than males for any given dose; the driving ability of females may therefore be particularly impaired.3 Zaleplon and the newer hypnotics acting at melatonin or serotonin receptors have not been found to have any negative residual effects on driving ability15 |
Lithium |
Lithium may impair visual adaptation to the dark2 but the implications for driving safety are unknown. Elderly people who take lithium may be at increased risk of being involved in an injurious motor vehicle crash16 |
Methylphenidate |
Some studies have demonstrated that reaction time is longer in patients with ADHD which may in turn be associated with increased driving risks.17 Other studies have found that methylphenidate improved driving performance in adults with ADHD,18 again suggesting that illness may make a bigger contribution to fitness to drive than the specific pharmacology of the treatment18 |
ADHD, attention deficit hyperactivity disorder; EPS, extrapyramidal side-effects; RTA, road traffic accident; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant. |
Many psychotropics can impair alertness, concentration and driving performance. Medicines that block H1, α1-adrenergic or cholinergic receptors may be particularly problematic. Effects are particularly marked at the start of treatment and after increasing the dose. Drivers must be made aware of any potential for impairment and advised to evaluate their driving performance at these times. They must stop driving if adversely affected.27 The use of alcohol will further increase any impairment. Many antipsychotics and antidepressants lower the seizure threshold. The DVLA advises this is taken into consideration when prescribing for a driver. Further information about the effects of psychotropics on driving can be found in Table 8.14.
Table 8.15 Summary of DVLA regulations for psychiatric disorders (November 2013)20
To be read in conjunction with the section on 'Driving and psychotropic medicines'. It is the illness rather than the medication which is of prime importance. For cases which involve more than one condition, please consider all relevant regulations. Any psychiatric condition which does not fit neatly into the classifications below should be reported to the DVLA if it is felt that it could affect safe driving. DVLA notification by licence holder or applicant is required except where indicated. |
||||
Diagnosis |
Group 1 Entitlement (cars and motorcycles) |
Group 2 Entitlement (heavy goods or public service vehicles) |
||
Notify DVLA? |
Notes |
Notify DVLA? |
Notes |
|
Uncomplicated anxiety or depression (without significant memory or concentration problems, agitation, behaviouraldisturbance or suicidal thoughts) |
No |
Consider effects of medication (see Table 8.14) |
No |
Very minor short-lived illnesses need not be notified to DVLA. Consider effects of medication (see Table 8.11) |
Severe anxiety states or depressive illnesses (with significant memory or concentration problems, agitation, behavioural disturbance or suicidal thoughts) |
Yes |
Driving should cease pending the outcome of medical enquiry. A period of stability will be required before driving can be resumed |
Yes |
Driving may be permitted when person is well and stable for 6 months or if the illness is longstanding but maintained symptom free on medication which does not impair driving. DVLA may require psychiatric reports |
Acute psychotic disorders of any type |
Yes |
Driving must cease during the acute illness. Relicensing can be considered when all of the following conditions can be satisfied:
Drivers with a history of instability and/or poor compliance will require a longer period off driving |
Yes |
DRIVING MUST CEASE pending the outcome of medical enquiry by the DVLA panel. The normal requirement is that the person be well and stable for 3 years before driving can be resumed, on minimum effective antipsychotic dose, optimal tolerability achieved with no associated deficits that might impair driving ability. The risk if relapsed, treated or untreated should be appraised as low. DVLA will require a consultant report specifically addressing these issues before the licence can be considered |
Hypomania/mania |
Yes |
See 'Acute psychotic disorders of any type' Repeated changes of mood: when there have been four or more episodes of mood swing in the last 12 months, at least 6 months' stability is required under condition(a) above |
Yes |
As above |
Chronic schizophrenia and other chronic psychoses |
Yes |
See 'Acute psychotic disorders of any type' Continuing symptoms, even with limited insight do not necessarily preclude driving. Symptoms should be unlikely to cause significant concentration problems, memory impairment or distraction whilst driving. Particularly dangerous are those drivers whose psychotic symptoms relate to other road users |
Yes |
As above |
Dementia or any organic brain syndrome |
Yes |
Patient should inform DVLA (see Table 8.14). Decision regarding fitness to drive subject reports. In early dementia, licence may be issued based on medical reports subject to annual review. A formal driving assessment may be necessary |
Yes |
Refuse or revoke licence |
Learning disability |
Yes |
Severe learning disability -licence application will be refused. Mild learning disability -possible if no relevant problems. Necessary to demonstrate adequate functional ability at the wheel: liaise with DVLA |
Yes |
Refusal or revocation if severe. Only persons with minor degrees of learning disability will be considered for a licence. When the condition is stable and there are no medical or psychiatric complications, licence may be restored |
Developmental disorders including Asperger's syndrome, autism, severe communication disorders and ADHD |
Yes |
Diagnosis not in itself a bar to licensing. Factors such as impulsivity, lack of awareness of the impact of own behaviour on self or others need to be considered |
Yes |
Continuing minor symptomatology may be compatible with licensing. Cases considered individually |
Behaviour disorders (e.g. violent behaviour) |
Yes |
Licence revoked if behaviour is seriously disturbed. Licence reissued only after behaviour has been satisfactorily controlled. Medical report required |
Yes |
If behaviour is seriously disturbed, licence refused/revoked. Restoration of licence possible if psychiatric reports confirm stability |
Personality disorders |
Yes |
If likely to be a source of danger at the wheel, licence would be revoked or refused. Can be permitted subject to medical report |
Yes |
Refusal/revocation if behaviour is likely to be a source of danger at the wheel. Restoration possible after psychiatrist's report confirms stability |
Alcohol misuse 'persistent misuse of alcohol confirmed by medical enquiry' |
Yes |
Licence refused/revoked for confirmed, persistent alcohol misuse until minimum of 6 months' controlled drinking or abstinence attained. Patient to seek advice from medical or other sources during period off the road |
Yes |
Same as Group 1 except 1 year's controlled drinking or abstinence required. Patient to seek advice from medical or other sources during period off the road |
Alcohol dependency (may include history of withdrawal symptoms, tolerance, detoxification(s) and/or alcohol-related fits) |
Yes |
Licence refused/revoked until a 1-year period free from alcohol problems attained. Abstinence usually required. Medical reports required. Restoration will require medical reports and may require independent medical examination and blood tests by DVLA. Consultant support/referral may be necessary |
Yes |
Licence not granted if there is a history of alcohol dependency in the past 3 years. Additional restrictions if seizures occur. Medical reports required. Restoration will require medical reports and may require independent medical examination and blood tests by DVLA. Consultant support/referral may be necessary |
Alcohol-related seizures |
Yes |
Following an isolated seizure, licence is revoked for a minimum 6 months. If relevant, refer to alcohol dependency above. If more than one seizure, then epilepsy regulations will apply. Medical enquiry will be required before restoration. Independent medical assessment by DVLA normally necessary |
Yes |
Following an isolated seizure, licence is revoked/refused for a minimum of 5 years. Restoration subject to:
If more than one seizure or underlying structural abnormality, vocational epilepsy regulations apply |
Alcohol-related disorders (e.g. hepatic cirrhosis with neuropsychiatric impairment or psychosis) |
Yes |
Licence refused/revoked until satisfactory recovery and medical standards are satisfied |
Yes |
Licence refused/revoked |
Drug misuse and dependency: cannabis, amfetamines, ecstasy, ketamine and other psychoactive substances |
Yes |
If persistent use or dependency confirmed, licence is refused or revoked until a minimum 6 months drug-free period. For ketamine misuse, 6 months off driving, drug free and 12 months if dependent. Assessment and urine screen arranged by DVLA may be required |
Yes |
If persistent use or dependency, refusal or revocation for a minimum of 1 year drug free. Assessment and urine screen arranged by DVLA will be required |
Heroin, morphine, methadone, cocaine methamfetamine |
Yes |
As above but for minimum of 1 year. Medical report may also be required on reapplication. (there are exceptions for those on a supervised maintenance programme) |
Yes |
As above but for a minimum of 3 years Medical report will also be required before relicensing (there are exceptions for those on a supervised maintenance programme) |
Many psychotropics are sedating. The more sedating a medicine is, the more likely it is to impair driving ability. Other medicines, either prescribed or bought over the counter, may also be sedative and/or affect driving ability (e.g. antihistamines5). One study found that 89% of patients taking other psychotropics in addition to antidepressants failed a battery of 'fitness to drive' tests.28 Since the degree of sedation any individual will experience is very difficult to predict, patients prescribed sedating medicines should be advised not to drive if they feel sedated.
It is the legal responsibility of the licence holder or applicant to notify the DVLA of any medical condition which may affect safe driving. A list of relevant medical conditions can be found in the DVLA'At a glance' guide.20 Drivers must recognize signs of impaired driving performance due to medication or illness.
Make sure the patient understands that their condition may impair their ability to drive. If the patient is incapable of understanding, notify the DVLA immediately. Explain to the patient that they have a legal duty to inform the DVLA.
Note: the DVLA guidance specifies that patients under S17 of the Mental Health Act must be able to satisfy the standards of fitness for their respective conditions and be free from any effects of medication which would affect driving adversely, before resuming driving. Very few patients will fulfil these criteria.
In mental health settings, it is common for patients to refuse medication. Some patients with cognitive disorders may lack capacity to make an informed choice about whether medication will be beneficial to them or not. In these cases, the clinical team may consider whether it would be in the patient's best interests to conceal medication in food or drink. This practice is known as covert administration of medicines. Guidance from the Nursing and Midwifery Council1–3 and the Royal College of Psychiatrists4 exists in order to protect patients from the unlawful and inappropriate administration of medication in this way. The legal framework for such interventions would be either the Mental Capacity Act (MCA)5 or, more rarely, the Mental Health Act (MHA).6
When it applies to the covert administration of medicines, the assessment of capacity regarding treatment is primarily a matter for doctors treating the patient.5,7 Nurses will also have to be mindful of their own codes of professional practice and should be satisfied that the doctor's assessment is reasonable. In assessing capacity it is important to make the assessment in relation to the particular treatment proposed. Capacity can vary over time and the assessment should be made at the time of the proposed treatment. The assessment should be documented in the patient's notes and recorded in the care plan.
A patient is presumed to have the capacity to make treatment decisions unless he/she is unable to:
If a patient has the capacity to give a valid refusal to medication and is not detainable under the Mental Health Act, their refusal should be respected.
If a patient has the capacity to give a valid refusal and is either being treated under the Mental Health Act or is legally detainable under the Act, the provisions of the Mental Health Act with regard to treatment will apply, which are outside the scope of this chapter. In general, the Mental Health Act will only be used if the person is actively resisting admission and treatment. Someone who passively assents to admission and treatment can be admitted and treated without the Mental Health Act being used. If such a patient lacks capacity, the legal framework under which the patient is being treated is the Mental Capacity Act.
The administration of medicines to patients who lack the capacity to consent and who are unable to appreciate that they are taking medication (e.g. unconscious patients) should not need to be carried out covertly.
However, some patients who lack the capacity to consent would be aware, if they were not deceived into thinking otherwise.8 For example a patient with moderate dementia who has no insight and does not believe he needs to take medication, but will take liquid medication if this is mixed with his tea without him being aware of this. It is this group to whom the rest of this guidance will apply.
Treatment may be given to people who lack capacity if it has been concluded that that treatment is in the patient's best interests (Section 5, MCA5) and proportionate to the harm to be avoided (Chapter 6.41, MCA Code of Practice.8) So, there should be a clear expectation that the patient will benefit from covert administration, and that this will avoid significant harm (either mental or physical) to the patient or others. The treatment must be necessary to save the patient's life, to prevent deterioration in health or to ensure an improvement in physical or mental health.8
The decision to administer medication covertly should not be made by a single individual but should involve discussion with the multidisciplinary team caring for the patient and the patient's relatives or informal carers. It is good practice to hold a 'best interests meeting'9 (see below). Decisions should be carefully documented and each instance of covert administration recorded on the prescription chart.10 The decision should be subject to regular review,8 and the reviews also documented.
The process for covert administration of medicines should include the following safeguards.
Haw C et al. Covert administration of medication to older adults: a review of the literature and published studies. J Psychiatr Ment Health Nurs 2010; 17:761–768.
Haw C et al. Administration of medicines in food and drink: a study of older inpatients with severe mental illness. Int Psychogeriatr 2010; 22:409–416.
Mental Welfare Commission for Scotland. Good Practice Guide: Covert administration. 2013.
http://www.mwcscot.org.uk/media/140485/covert_medication_finalnov_13.pdf