Antipsychotics and their adverse effects

• Antipsychotic drugs reduce or remove psychotic symptoms such as hallucinations, delusions and disorganised thought. Every member of the class acts on brain dopamine, above all by blocking dopamine D2 receptors.
• The class is split into two generations. Typical (first-generation, conventional) drugs such as haloperidol block D2 receptors strongly and predictably produce extrapyramidal movement disorders. Atypical (second-generation) drugs such as risperidone and olanzapine also block serotonin 5-HT2A receptors and carry a lower short-term risk of movement disorders, but a higher risk of weight gain and metabolic disease.
• The feared acute complications are extrapyramidal syndromes (acute dystonia, akathisia, parkinsonism, tardive dyskinesia) and neuroleptic malignant syndrome. The feared long-term complications are metabolic syndrome, QT prolongation, hyperprolactinaemia, tardive dyskinesia and, for clozapine, agranulocytosis.
• The cure for most problems is prevention: start low and titrate slowly, use the lowest effective dose, monitor movement disorders, weight, blood pressure, glucose and lipids on a fixed schedule, and intervene early.
• Clozapine is reserved for treatment-resistant schizophrenia but is the most effective antipsychotic; it needs regular absolute neutrophil count monitoring and has the best evidence for reducing suicide risk.

By the end of this page you should be able to:

1. Name the typical and atypical antipsychotics and say what receptor actions define each group.
2. Explain why D2 blockade treats psychosis and why it also causes movement disorders, hyperprolactinaemia and (rarely) neuroleptic malignant syndrome.
3. Recognise and manage acute dystonia, akathisia, parkinsonism, tardive dyskinesia and neuroleptic malignant syndrome.
4. Describe the baseline and follow-up monitoring for weight, cardiovascular and metabolic risk on antipsychotic treatment.
5. State how clozapine is titrated and monitored, including the neutropenia and myocarditis risks.
6. Identify interactions, contraindications, pregnancy warnings and common exam traps.

Antipsychotics (also called neuroleptics or major tranquillisers) are the drug treatment of severe mental disorders in which reality testing is impaired: schizophrenia, schizoaffective disorder, bipolar mania, severe depressive psychosis and drug-induced psychosis. Used well, they let people return to work, relationships and independent life. Used carelessly, they cause stiffness that looks like Parkinson disease, sudden muscle spasms that frighten patients, weight gain that drives diabetes and, occasionally, fatal syndromes.

This page is written for a prescriber meeting the class for the first time. It covers the mechanism that unites all members, the members themselves and how they are dosed, when to use them, what goes wrong and why, how to monitor and prevent harm, the special situations (pregnancy, renal or hepatic impairment, interactions) and the points examiners test.

Typical, or first-generation, antipsychotics are strong D2 receptor blockers with relatively little serotonin blockade. They are very effective against hallucinations and delusions but, because they block roughly 60 to 80 percent of striatal D2 receptors at clinically useful doses, they frequently produce extrapyramidal movement disorders.

Representative agents and customary oral daily dose ranges include:

• Haloperidol 0.5 to 2 mg twice or three times daily for moderate symptoms, or 3 to 5 mg twice or three times daily for severe symptoms, with occasional use of up to 100 mg/day in resistant illness. Long-acting decanoate preparations are given by intramuscular injection. The haloperidol label also gives anticholinergic cautions and QT warnings.^[4]
• Chlorpromazine, fluphenazine, trifluoperazine, perphenazine and thioridazine: older agents, now less used in many settings, with lower potency and more anticholinergic (and, for thioridazine, QT) liability.
• Benperidol and sulpiride are used in some regions; sulpiride is a selective D2/D3 antagonist with a relatively low movement-disorder burden at low doses.

Atypical, or second-generation, antipsychotics are defined by combined serotonin 5-HT2A and dopamine D2 receptor blockade (a higher 5-HT2A than D2 affinity) with looser, more rapidly dissociating D2 binding. This serotonergic antagonism is thought to increase dopamine release in the striatum, which protects against extrapyramidal symptoms.^[3]

Modern members, with dose and pharmacology from the same source, are:

• Risperidone using 4 to 6 mg/day as a commonly cited therapeutic dose in schizophrenia. It is a strong 5-HT2A and D2 blocker with high alpha-adrenergic activity; extrapyramidal effects are dose-related and above about 6 mg/day they begin to resemble those of typical agents.^[3]
• Paliperidone, the active metabolite of risperidone, given as an extended-release tablet (dopamine D2 occupancy about 70 to 80 percent at 6 to 9 mg/day) or as a monthly depot.^[3]
• Olanzapine 5 to 30 mg once daily (commonly 10 to 20 mg). It combines strong 5-HT2A, 5-HT2C, histamine H1 and muscarinic effects with a low acute extrapyramidal burden, and is one of the most metabolically aggressive agents.^[3]
• Quetiapine is titrated rapidly because of sedating histamine and alpha effects; dopaminergic effects are relatively modest at standard doses. Therapeutic drug monitoring proposes 70 to 170 ng/mL.^[3]
• Amisulpride is a selective D2/D3 antagonist (preferential presynaptic blockade at low doses, postsynaptic at higher doses) with renal elimination and minimal cytochrome interactions; therapeutic plasma levels are around 367 ng/mL (proposed range 100 to 400).^[3]
• Ziprasidone 80 to 160 mg/day combines dopamine and 5-HT2A blockade with 5-HT1A agonism, serotonin and noradrenaline reuptake effects, and the smallest weight-gain liability among the older atypicals.^[3]
• Aripiprazole 5 to 30 mg/day is a partial agonist at D2 and 5-HT1A and an antagonist at 5-HT2A, sometimes called a dopamine-serotonin stabiliser. At 10 mg/day, striatal D2 occupancy is roughly 87 to 93 percent, and at least 60 percent D2 occupancy appears necessary for control of psychotic symptoms; it does not greatly raise prolactin.^[3]
• Asenapine, iloperidone, lurasidone and cariprazine are newer agents with varying receptor fingerprints; iloperidone is titrated to 12 to 24 mg/day because of alpha-1 adrenergic blockade, and lurasidone 20 to 160 mg is taken with food.^[3]
• Clozapine is discussed separately below.

A useful shorthand for examinations:

• Typical agent equals strong, tight D2 blockade equals high movement-disorder risk and low weight-gain risk.
• Atypical agent equals D2 plus 5-HT2A blockade with looser binding equals lower movement-disorder risk but higher metabolic risk (especially clozapine and olanzapine).

The dopamine hypothesis of schizophrenia proposes that overactivity of dopamine transmission in certain brain pathways produces positive symptoms (hallucinations, delusions, disorganisation). All antipsychotics block D2 receptors, and no drug has been shown to act as an antipsychotic without significant D2 affinity. PET studies confirm that clinical response is associated with blockade of roughly 60 to 80 percent of brain D2 receptors.^[3][4]

The relevant receptor actions are:

• D2 blockade in the mesolimbic pathway (midbrain to limbic areas) reduces positive symptoms.
• D2 blockade in the nigrostriatal pathway (midbrain to striatum) produces extrapyramidal movement disorders. Atypical drugs reduce this via 5-HT2A antagonism, which increases striatal dopamine release.
• D2 blockade in the tuberoinfundibular pathway (hypothalamus to pituitary) removes dopamines normal brake on prolactin, producing hyperprolactinaemia.
• D4 and 5-HT2A effects are especially prominent with clozapine and may contribute to benefit in negative symptoms and treatment resistance; clozapine uniquely combines relatively high D1, low D2 and very high 5-HT2 occupancy.^[3]
• Muscarinic, histamine (H1) and alpha-adrenergic blockade explain sedation, weight gain, orthostatic hypotension, anticholinergic effects and dry mouth.

Three explanations for atypical action (loose D2 binding with rapid dissociation, dopamine-serotonin antagonism and preferential limbic D2 binding) have been proposed; in practice the clinical distinction is what matters most.^[3]

• Most antipsychotics are extensively metabolised by hepatic cytochrome P450 enzymes, so potent inhibitors or inducers change levels dramatically (see Interactions). Clozapine is metabolised by CYP1A2, CYP2D6 and CYP3A4; smoking induces CYP1A2 and lowers clozapine levels.
• Most are highly protein-bound with large volumes of distribution and long half-lives, permitting once-daily dosing.
• Peak plasma levels occur within hours; steady state is reached within days to weeks.
• Depot (long-acting injectable) formulations exist for haloperidol, fluphenazine, zuclopenthixol, risperidone, paliperidone, olanzapine and aripiprazole.
• Clozapine reaches steady state in 7 to 10 days; plasma levels of 350 to 420 ng/mL are associated with an increased probability of response. Therapeutic drug monitoring proposes 20 to 50 ng/mL for olanzapine, 70 to 170 ng/mL for quetiapine, 100 to 400 ng/mL for amisulpride; ziprasidone remains largely undetermined.^[3]

• Schizophrenia and schizoaffective disorder: antipsychotics are first-line pharmacological treatment, combined with psychosocial rehabilitation, cognitive behavioural therapy and family intervention. NICE recommends oral antipsychotic medication plus psychological interventions for first-episode and acute episodes.^[1]
• Treatment-resistant schizophrenia (failure of at least two adequate trials of different antipsychotics, one being a non-clozapine second-generation drug): clozapine.^[1]
• Bipolar mania and mixed episodes: antipsychotics with mood-stabilising action (olanzapine, quetiapine, risperidone, aripiprazole, asenapine, cariprazine, haloperidol), following the relevant bipolar guideline.
• Severe depressive psychosis, delusional disorder, persistent delusional states and acute and transient psychotic disorders.
• Tourette syndrome and severe behavioural disturbance in young people (haloperidol, risperidone).
• Short-term control of severe agitation, aggression and self-harm in any setting, with close monitoring.
• Antiemetic and prokinetic uses of low-dose agents such as prochlorperazine (outside the scope of this page).

Antipsychotic drugs should not be used simply to control behaviour in dementia-related psychosis. In elderly people with dementia they increase mortality (heart failure, sudden death, pneumonia).^[2][4]

General principles (NICE CG178, last updated 4 September 2026):^[1]

• Discuss and record the side effects the person is most willing to tolerate, and the expected benefit and timeline.
• Start at the lower end of the licensed range and titrate slowly within the dose ranges given in the BNF or SPC.
• Carry out an explicit therapeutic trial at an adequate dose for 4 to 6 weeks. ^[1]
• Do not use rapid neuroleptisation: no high, repeated or rapidly escalated doses for an acute episode.
• Do not initiate routine combined (two or more) antipsychotics except for short periods such as a cross-taper.
• Justify and record any dose outside the BNF or SPC range.
• Assess antipsychotic response with structured instruments; review medication annually.

Clozapine titration, from the CLOZARIL label:^[2]

• Start 12.5 mg once or twice daily (because of orthostatic hypotension risk).
• If tolerated, increase by 25 to 50 mg/day to a target of 150 to 225 mg twice daily by the end of week 2. ^[2]
• Thereafter increase by up to 100 mg once or twice weekly. ^[2]
• Maximum 450 mg twice daily (900 mg/day); in practice 300 to 450 mg/day is a common maintenance target. ^[2]
• If a dose is missed: if 1 day is missed, restart at 40 to 50 percent of the previous dose; if 2 days are missed, at about 25 percent; after a longer gap, restart at 12.5 mg once or twice daily. ^[2]

Long-acting injectable (depot) dosing is based on the equivalent oral daily dose at the correct interval and must follow each products monograph and local protocol.

Children and adolescents: use half or a third of the adult starting dose and titrate slowly within BNF or SPC ranges. Haloperidol is licensed from age 3 years, with oral doses of 0.05 to 0.15 mg/kg/day for psychotic disorders. Risperidone, paliperidone, aripiprazole and olanzapine have licensed paediatric schedules in their monographs. Clozapine is generally reserved for adolescents who have failed other agents, on a consultant's direction.^{[1][4] [3]}

Antipsychotic adverse effects fall into five groups that map onto receptor actions: movement (D2), prolactin (D2), cardiovascular and metabolic (muscarinic, histamine, metabolic), autonomic and cholinergic, and allergic or immunological (clozapine-specific).

These are the signature adverse effects of D2 blockade, especially with typical, high-potency agents, although any antipsychotic can produce them at sufficient dose.

Risk factors for movement disorders include high doses, rapid titration, older age (except acute dystonia, which is more common in the young), female sex for tardive dyskinesia, a prior episode, organic brain disease and concurrent anticholinergic load. The haloperidol label notes that persistent extrapyramidal symptoms sometimes do not respond, and the drug may have to be withdrawn.^[4]

NMS is a rare but potentially fatal idiosyncratic reaction, classically described with typical, high-potency agents but reported with atypicals too. It is more a clinical diagnosis than a laboratory one.

Features, from product labelling and guidelines:

• High fever, generalised muscle rigidity ("lead pipe"), altered mental state (confusion, stupor, catatonia) and autonomic instability (tachycardia, irregular blood pressure, diaphoresis, cardiac arrhythmia) are the core.
• Elevated creatine kinase, myoglobinuria and acute renal failure reflect muscle breakdown; leukocytosis is common.^[4]
• Onset is usually in the first few weeks, often after a dose increase, but can occur at any time.

Management:

1. Stop the antipsychotic and all non-essential central nervous system drugs immediately.
2. Supportive care in a monitored setting: fluids, cooling, correction of electrolytes, treatment of renal failure and of any infection.
3. There is no single agreed pharmacological protocol; bromocriptine (a dopamine agonist), dantrolene (for muscle rigidity and hyperthermia) and benzodiazepines are commonly used, based on case series.
4. Electroconvulsive therapy may be considered where other treatments fail and the psychiatric illness is severe.
5. Rechallenge with an antipsychotic, if unavoidable, must be delayed until recovery, at the lowest dose of a lower-risk (atypical) drug, with close supervision, because recurrence is reported.^[2][4]

Important differentials include untreated or inadequately treated extrapyramidal symptoms with intercurrent infection, central anticholinergic toxicity, heat stroke, drug fever, serotonin syndrome and primary central nervous system pathology.^[4]

Atypical antipsychotics (especially clozapine and olanzapine) are associated with weight gain and the metabolic syndrome, which includes central obesity, dyslipidaemia, hyperglycaemia and hypertension. Typical agents can also produce weight gain, but generally less. Some agents (aripiprazole, ziprasidone, lurasidone, asenapine, cariprazine) have a lower propensity.^[3]

Mechanisms include H1 and 5-HT2C antagonism (appetite and satiety), antimuscarinic effects, and downstream effects on insulin sensitivity and hepatic lipogenesis. Early, rapid weight gain in the first weeks of treatment predicts later weight gain and diabetes risk.

Antipsychotics prolong the cardiac action potential and the QT interval, predisposing to torsades de pointes and sudden death. The risk is higher with typical low-potency agents (thioridazine, haloperidol at high dose), with ziprasidone, and with any agent in the presence of electrolyte disturbance, hypothyroidism, congenital long QT, pre-existing heart disease, or other QT-prolonging or metabolism-inhibiting drugs. Even haloperidol has been associated with sudden death and torsades at high doses, and ECG changes have occurred at recommended doses in predisposed patients.^[2][4]

Clozapine carries a specific QT warning: discontinue if the QTc exceeds 500 ms. Correct potassium and magnesium before and during treatment, and avoid combining with other QT-prolonging drugs.^[2]

D2 blockade in the tuberoinfundibular pathway raises serum prolactin, especially with risperidone and paliperidone (and typical, high-potency agents such as haloperidol). Manifestations include galactorrhoea, menstrual disturbance, sexual dysfunction, infertility and, in the long term, osteopaenia. Olanzapine has a smaller effect, and aripiprazole and clozapine have little effect.^[3] Raised prolactin is also a potential worry in patients with a history of hormone-dependent cancer; the clinical significance is debated.

• Sedation and somnolence (H1 and alpha-1 effects): common with clozapine, olanzapine and quetiapine; advise about driving and machinery. Falls and fractures are a specific concern in elderly and debilitated patients.
• Orthostatic hypotension, bradycardia and syncope (alpha-1): risk is greatest during titration and with first doses; haloperidol and clozapine labels both warn of this. Clozapine can produce syncope at doses as low as 12.5 mg; initiate at 12.5 mg once or twice daily and titrate slowly in divided doses.^[2][4]
• Anticholinergic toxicity: dry mouth, blurred vision, constipation, urinary retention, cognitive slowing, paralytic ileus. Gastrointestinal hypomotility with clozapine can be fatal (ileus, obstruction, perforation); constipation must be treated actively, and anticholinergic drugs avoided where possible.^[2]
• Seizures: dose-related, especially with clozapine (cumulative incidence approximately 5%, crude rate 3.5% in pre-marketing trials) and high-dose typical agents; use caution in epilepsy and with other proconvulsant drugs.^[2][4]
• Hepatotoxicity: clozapine can cause fatal hepatitis or transaminase elevations; monitor liver function.^[2]
• Fever: prompt investigation for infection, neutropenia (clozapine), NMS or medication reaction.^[2]
• Eosinophilia (greater than 700 per microlitre, around 1 percent) with clozapine, which may herald myocarditis, pericarditis, nephritis, pancreatitis or colitis.^[2]
• Myocarditis, pericarditis and cardiomyopathy with clozapine; myocarditis and pericarditis most often present within the first 2 months, cardiomyopathy usually later, and all can occur at any time and may be fatal, usually needing permanent discontinuation.^[2]
• Pulmonary embolism, venous thrombosis and sialorrhoea (hypersalivation) are clozapine specific.

Severe neutropenia (absolute neutrophil count under 500 per microlitre) occurs most often in the first 18 weeks and can be fatal. Baseline ANC must be at least 1500 per microlitre (1000 for benign ethnic neutropenia, also known as Duffy-null associated neutrophil count). Monitoring intervals: weekly for the first 6 months, every 2 weeks from months 7 to 12, and monthly thereafter (more often if moderate or severe neutropenia, fever above 38.5 degrees C, or concomitant neutropenia-inducing drugs). See the clozapine label for dose modifications (interrupt for 500 to 999, discontinue below 500).^[2]

Before starting, take a full physical examination and consider an ECG if the SPC specifies one, if the patient has cardiovascular risk or disease, or if starting as an inpatient.^[1]

• Pharmacokinetic (CYP): clozapine is metabolised by CYP1A2, CYP2D6 and CYP3A4. Strong CYP1A2 inhibitors (fluvoxamine, ciprofloxacin, enoxacin) require the clozapine dose to be reduced to one third; strong CYP3A4 inducers (carbamazepine, phenytoin) are not recommended concomitantly. Stopping an inducer (including tobacco smoke) makes a previously stable dose toxic. Olanzapine levels rise with fluvoxamine and fall with carbamazepine and smoking. Haloperidol levels fall with rifampin (by about 70 percent in one study) and carbamazepine.^[2][4]
• QT: additive QT prolongation with macrolides, fluoroquinolones, methadone, ondansetron, tricyclics, other antipsychotics and electrolyte-wasting drugs.
• Anticholinergic burden: adding anticholinergics to clozapine risks ileus and cognitive impairment.
• Central nervous system depressants (alcohol, opioids, benzodiazepines): additive sedation and respiratory depression.
• Lithium plus a high-potency antipsychotic has been associated with an encephalopathic syndrome (confusion, fever, extrapyramidal signs, leukocytosis, elevated enzymes) with irreversible brain damage in some cases; if both are needed, monitor closely and stop promptly at neurological change.^[4]
• Anticonvulsants: most antipsychotics lower seizure threshold.
• Dopaminergic agents (levodopa in Parkinson disease) are antagonised; low-potency or atypical agents are preferred where antipsychotic treatment is unavoidable in Parkinson disease.

• Contraindications from individual labels: hypersensitivity (clozapine may be severe, including photosensitivity, vasculitis, erythema multiforme, Stevens-Johnson syndrome); haloperidol is contraindicated in Parkinson disease, severe central nervous system depression or coma, and hypersensitivity. Clozapine is not approved for dementia-related psychosis.^[2][4]
• Cardiovascular disease, cerebrovascular disease, QT prolongation, hypokalaemia, hypomagnesaemia, hypothyroidism, familial long QT are cautions rather than absolute contraindications, but drive the decision to obtain an ECG.^[2][4]
• Epilepsy and rhythm disorders: titrate slowly.
• Glaucoma (narrow angle), prostatic hypertrophy, urinary retention, constipation, paralytic ileus are cautions for anticholinergic agents; avoid combining anticholinergics with clozapine.
• Bone marrow or blood dyscrasia, prior clozapine-induced neutropenia, concomitant cytotoxic or bone-marrow-suppressing drugs are contraindications to clozapine.
• Pheochromocytoma and some endocrine tumours may interact with chlorpromazine.

Overdose exaggerates the pharmacological actions: deep sedation, hypotension, severe extrapyramidal reactions, QRS/QT changes, seizures, temperature changes and, occasionally, arrhythmias and coma. There is no specific antidote; treatment is supportive, with airway protection, fluid resuscitation, activated charcoal, ECG monitoring and treatment of QT prolongation (magnesium), extrapyramidal signs (anticholinergic) and seizures.^[4]

Agranulocytosis with clozapine is managed by stopping the drug immediately, haematology review and, for profound neutropenia, colony-stimulating factor and isolation. Management of neutropenia at lower counts follows the label table (interrupt at 500 to 999, discontinue below 500 per microlitre).^[2]

• Antipsychotics cross the placenta. Third-trimester exposure is associated with extrapyramidal and withdrawal symptoms in the neonate (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, feeding disorder), of variable severity. Use only if the potential benefit justifies the potential risk, and document the discussion.^[2][4]
• No increased rate of major malformations has been consistently shown for the commonly used agents (chlorpromazine, haloperidol, olanzapine, quetiapine, risperidone), but data are limited and are accumulating for newer agents.
• Clozapine may affect the neonate; it is generally continued only where benefits clearly outweigh risks, with neonatal monitoring.
• Prescribe the lowest effective dose, as monotherapy where possible, and arrange specialist obstetric and psychiatric input. Combinations with mood stabilisers or antidepressants for relapse prevention should be reviewed with the woman's preferences.
• Breastfeeding: most agents (including haloperidol, chlorpromazine, olanzapine) pass into breast milk in small amounts; if breastfeeding is preferred, use the lowest dose, feed before the dose, monitor the infant for sedation, feeding, movement or jaundice, and avoid clozapine (reported cases of agranulocytosis and sedation in infants).^[2][4]

• Haloperidol: lower starting doses in geriatric or debilitated patients; supervision for accumulation.
• Clozapine: in significant renal or hepatic impairment, or in CYP2D6 poor metabolisers, the dose may need to be reduced and monitoring intensified. Clozapine depends on hepatic metabolism; liver function should be checked if jaundice or transaminitis is suspected, and the drug stopped for hepatitis.^[2]
• Amisulpride is eliminated renally and needs dose adjustment in renal impairment. Paliperidone is renally cleared and requires dose reduction with reduced renal function.
• Most atypicals are metabolised hepatically; in hepatic impairment, titrate slowly and monitor. Obstructive jaundice and marked alcohol dependence increase risk.
• Elderly people are more sensitive to hypotension, sedation, parkinsonism, tardive dyskinesia and falls: start low and titrate slowly.^[4]

• Dementia-related psychosis: antipsychotics increase mortality in older people with dementia; avoid except for short-term, clearly justified treatment of severe distress, with regular review and evidence of benefit.^[2][4]
• Parkinson disease and Lewy body dementia: high sensitivity to extrapyramidal symptoms; if absolutely required for severe psychosis, use quetiapine or clozapine; avoid haloperidol and other high-potency typicals.
• Children: sedation, weight gain and extrapyramidal effects are common; use licensed, age-appropriate indications and monitor growth and cardiometabolic risk.
• Low-resource settings: if blood counts, glucose or lipids cannot be measured, use the mentally tested minimum of weight, pulse, blood pressure and a movement-disorder check at every visit, start low, avoid polypharmacy, keep treatment regimens simple, use depot only after oral tolerability is confirmed, document the reason, and identify which symptoms would trigger urgent referral (fever, sudden stiffness, collapse, marked weight change, pregnancy).

• Thinking "atypical equals no movement disorders": risperidone above about 6 mg/day acts like a typical agent; all antipsychotics can cause tardive dyskinesia and NMS. ^[3]
• Equating akathisia with worsening psychosis and raising the dose: this makes the patient worse.
• Missing NMS because of fever attributed to infection: remember rigidity plus altered mental state.
• Forgetting that stopping smoking raises clozapine (and olanzapine) levels.
• Forgetting baseline and scheduled metabolic monitoring, including waist circumference (not just weight) and lipids.
• Forgetting the 4 to 6 week trial at adequate dose before calling a drug a failure.
• Forgetting that antipsychotic withdrawal should be gradual, with 2 years of follow-up for relapse monitoring. ^[1]
• Calling a first episode of psychosis "treatment-resistant" without two failed adequate trials of different agents.
• Prescribing anticholinergics long term for extrapyramidal effects, which worsens tardive dyskinesia and cognition.
• Using antipsychotics in pregnancy without documenting the risk-benefit discussion, or in dementia without justification.

• All antipsychotics block brain D2 receptors; clinical response is associated with blockade of roughly 60 to 80 percent of D2 receptors.
• Typical (first-generation) agents are strong D2 blockers with high extrapyramidal liability but generally lower metabolic risk; atypical (second-generation) agents combine 5-HT2A and D2 blockade with lower movement-disorder risk but greater weight-gain and metabolic risk.
• Acute dystonia responds urgently to anticholinergics; akathisia must not be treated by raising the dose; parkinsonism is treated by reducing or switching with anticholinergics if needed; tardive dyskinesia is best prevented and may improve by switching to clozapine.
• Neuroleptic malignant syndrome is fever plus rigidity plus altered mental state plus autonomic instability; stop the drug and give intensive supportive care.
• Metabolic monitoring includes weight weekly for 6 weeks then at 12 weeks, 1 year and annually, with waist circumference, blood pressure, glucose or HbA1c and lipids on a fixed schedule. ^[1]
• QT risk is increased by high doses, electrolyte disturbance, other QT-prolonging drugs and predisposing heart disease; clozapine is discontinued if QTc exceeds 500 ms.
• Clozapine is for treatment-resistant schizophrenia, needs slow titration (12.5 mg to 150 to 225 mg twice daily by 2 weeks, maximum 900 mg/day), neutrophil monitoring, and warns of myocarditis, seizure, gastrointestinal hypomotility and metabolic effects. ^[2]
• Pregnancy: third-trimester exposure causes neonatal extrapyramidal or withdrawal symptoms; use the lowest effective dose and document the discussion; clozapine is generally avoided in breastfeeding.

Antipsychotic adverse effects are most safely learned alongside schizophrenia and bipolar disorder diagnosis and treatment, movement disorders, QT prolongation, diabetes, metabolic syndrome and pregnancy prescribing. Link these with the MedGrasp topics for your setting.