Psychotropic Adverse Effects

Antipsychotic-specific adverse effects, mostly relevant to second-generation agents. For drug-specific dosing, see eTG/AMH (subscription — cite by name only).

Weight gain and cardiometabolic effects

Antipsychotics vary in their cardiometabolic risk (weight gain, dyslipidaemia, hyperglycaemia, hypertension). Among second-generation agents, clozapine and olanzapine carry the highest risk, followed by quetiapine. Just under 50% of people with psychosis in Australia meet criteria for metabolic syndrome — increased waist circumference plus any two of: raised triglycerides, reduced HDL, hypertension, hyperglycaemia.

Start monitoring cardiometabolic risk factors immediately after an antipsychotic is started, then every three months during the first year, then every six months after that. A package of care comprising aerobic exercise, weight loss, smoking cessation, consuming a high soluble fibre diet, reducing alcohol intake and potentially adding omega-3 fish oils may lead to significant improvements in cardiovascular risks. If the patient is becoming increasingly metabolically compromised, but their psychiatric history supports continuing their current medication, it may be wise to enhance the lifestyle modification as much as possible — a switch should still only follow consultation with a psychiatrist, and clozapine in particular is rarely switchable given it’s usually reserved for treatment-resistant illness.

Hyperprolactinaemia

Raised prolactin can cause gynaecomastia, galactorrhoea, menstrual disturbance, anovulation, impaired spermatogenesis, decreased libido, impaired arousal, impotence, and anorgasmia — and can reduce bone mineral density, a particular concern in young patients or those with osteoporosis. Effects are often unacceptable to patients. Risperidone/paliperidone and amisulpride carry particular risk.

If dose reduction isn’t practical or effective, switch to an antipsychotic with lower hyperprolactinaemia risk. If switching isn’t advisable, adding low-dose aripiprazole (5 mg daily) has been reported to lower prolactin.

QTc prolongation

Many antipsychotics prolong the QTc interval, risking life-threatening arrhythmia (torsades de pointes). Obtain a baseline ECG, then check annually. Avoid combining drugs that are each independently known to prolong QTc. If QTc > 450/470–500 ms or has increased more than 30–60 ms, switch to another antipsychotic.

Sedation

Occurs with all antipsychotics at sufficient dose, often worse initially or after a dose increase. Warn patients about the effect on driving/operating machinery. Relative risk: chlorpromazine and clozapine (highest); olanzapine and quetiapine (moderate).

Orthostatic hypotension

Common with many agents, particularly risperidone and paliperidone — start these at a low dose. Switch to a different antipsychotic if the effect is severe/persistent.

Anticholinergic effects

More likely with clozapine, chlorpromazine, and pericyazine: dry mouth, blurred vision, raised intraocular pressure, constipation, urinary hesitancy. Older patients are more sensitive to central anticholinergic effects (e.g. delirium).

Movement disorders (extrapyramidal effects)

Acute dystonia — sustained or brief muscle contraction causing twisting movements or abnormal postures, usually within minutes to days, affecting the face/neck/trunk (including laryngospasm, oculogyric crisis). Treat with benztropine 1–2 mg IV/IM as a single dose, then switch to the lowest effective oral dose and stop within a few weeks; consider a dose reduction or switch of the causative antipsychotic.

Parkinsonism — typically emerges in the early weeks of first-generation antipsychotic treatment. Reduce the dose or switch to a second-generation agent; benztropine 0.5–2 mg orally daily can help.

Tardive dyskinesia — a chronic movement disorder with repetitive involuntary choreiform movements, particularly of the tongue/lips/mouth, but potentially affecting any body part. If it occurs, switch to another antipsychotic (specifically a second-generation agent, or clozapine); refer to a movement-disorder specialist if treatment is needed.

Akathisia — an uncomfortable restlessness with an urge to move. Reduce the dose or switch to a second-generation agent; short-term options include propranolol 20–40 mg orally 3–4 times daily, or diazepam 2–5 mg orally 3 times daily.