3 Clinical psychopharmacology3.4 Therapeutics
3.4.1.2.3 Physical health status and co prescribed medications
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Written by Resident Doctor Committee · Published
The physical and medication history
Record diagnoses, adverse drug reactions and any family history of sudden death or drug intolerance.
Ask about falls, syncope, seizures, constipation and sleep apnoea (snoring with daytime sleepiness), which raises sedative risk.
List every medicine, including as-required drugs, depots, other services' prescriptions, pharmacy products, supplements, alcohol, tobacco and recreational drugs.
Ask about recently stopped drugs, because irreversible monoamine oxidase inhibitor effects and enzyme induction persist after withdrawal.
St John's wort induces cytochrome P450 3A4 (CYP3A4) and adds serotonergic effects.
Comorbidity that changes choice
Severe mental illness carries a 15 to 20 year mortality gap, and cardiovascular disease is a major preventable cause.
System | Effect |
|---|---|
Cardiovascular | QT risk rises with syncope, long QT, structural or conduction disease, and low potassium or magnesium |
Respiratory | Chronic obstructive pulmonary disease, neuromuscular weakness and untreated sleep apnoea raise risk, especially with opioids plus benzodiazepines |
Hepatic | Reduced metabolism, low albumin and portosystemic shunting alter exposure |
Renal | Lithium, gabapentinoids, amisulpride, sulpiride and paliperidone accumulate; dehydration or acute kidney injury quickly causes toxicity |
Neurological | Dopamine blockade worsens parkinsonism; antimuscarinics cause delirium |
Baseline investigations
Risk | Baseline |
|---|---|
Metabolic | Weight, waist, blood pressure, glucose or glycated haemoglobin, lipids |
Cardiac | Pulse, potassium, magnesium, electrocardiogram where indicated |
Haematological | Full blood count, clozapine monitoring service registration |
Movement and cognitive | Abnormal movements, gait, cognition, falls |
A normal baseline does not remove future risk.
Pharmacokinetic interactions
Tobacco smoke, not nicotine, induces CYP1A2, so stopping smoking can raise clozapine and olanzapine levels within days, including on smoke-free wards.
Inhibition acts quickly, but induction develops and wears off over weeks: levels fall after starting carbamazepine and rise after stopping it.
Low albumin raises the free fraction of highly bound drugs, so a low total valproate level may hide excessive active drug.
Frailty increases adverse effects without changing drug levels.
Cumulative pharmacodynamic burden
Drugs can add to one adverse effect without changing each other's levels.
Burden | Contributors | Result |
|---|---|---|
Sedation | Antipsychotic, opioid, benzodiazepine, gabapentinoid, alcohol | Hypoventilation, aspiration |
Postural hypotension | Tricyclic, antihypertensive, tamsulosin, trazodone | Falls, fracture |
Antimuscarinic load | Tricyclic, oxybutynin, procyclidine, hyoscine | Retention, delirium |
QT prolongation | Two QT-prolonging drugs, diuretic hypokalaemia, bradycardia | Torsade de pointes |
Bleeding | Selective serotonin reuptake inhibitor with anti-inflammatory, aspirin or anticoagulant | Gastrointestinal haemorrhage |
Seizure threshold | Clozapine, bupropion, tramadol, tricyclic, alcohol withdrawal | Seizure |
Serotonergic load | Antidepressant with tramadol, linezolid, triptan, lithium | Serotonin toxicity |
Anticholinergic burden scales measure the cumulative antimuscarinic load.
Medicines that cause psychiatric symptoms
Drug | Effect |
|---|---|
Corticosteroids | Mania, depression, psychosis; risk rises steeply above 40 mg prednisolone daily |
Dopamine agonists | Hallucinations, impulse control disorders |
Levetiracetam | Irritability, aggression |
Interferon | Depression |
Isotretinoin, montelukast, mefloquine, varenicline | Neuropsychiatric effects |
Diabetes does not automatically exclude clozapine; monitoring is matched to risk.
Prescribing cascades
A prescribing cascade treats an adverse effect as a new illness, as when akathisia prompts a higher antipsychotic dose.
Drug-induced parkinsonism may lead to procyclidine, then to treatments for constipation and confusion.
A diuretic for calcium channel blocker oedema can cause hypokalaemia and raise antipsychotic QT risk.
Reassessment
Reassess after acute illness, dehydration, large weight change, altered smoking, interacting drug changes or admission.