Overview of antipsychotic adverse effects

Solmi 2017 Pillinger 2020

Adverse effects occur commonly with antipsychotics. The frequency of occurrence depends on the antipsychotic; see Approximate relative frequency of common adverse effects of antipsychotics for approximate relative antipsychotic adverse effect frequency.

Note: It is crucial to reduce the impact and incidence of antipsychotic adverse effects.

It is crucial to reduce the impact and incidence of antipsychotic adverse effects by taking the following measures.

Before starting antipsychotic therapy, to guide antipsychotic choice:

inform the patient about potential adverse effects and how they are monitored, prevented or addressed, and discuss which adverse effects are acceptable to them
consider the propensity for an antipsychotic to cause adverse effects in the context of the patient’s comorbidities and baseline parameters potentially affected by antipsychotic therapy. For example:
- avoid antipsychotics that significantly increase cardiometabolic risk in patients who are overweight, at high risk of cardiovascular disease or have a family history of diabetes
- avoid antipsychotics likely to cause QT-interval prolongation in patients at risk
- avoid antipsychotics likely to cause orthostatic hypotension, anticholinergic adverse effects and sedation in older people, and patients who are cognitively impaired or at risk of falls
- consider the adverse effect profile of other drugs the patient takes; if possible, do not combine an antipsychotic with a drug that has similar adverse effects
- consider the potential for interactions with other drugs the patient takes; if possible, do not combine an antipsychotic with a drug that inhibits its metabolism¹.

During antipsychotic therapy:

regularly monitor for adverse effects—#ptg8-c73-s1__tptg8-c73-tbl4 provides a suggested monitoring schedule
regularly remind the patient to eat a healthy diet² and undertake physical activity³
regularly ask about smoking status and, if relevant, encourage smoking cessation—this may increase the concentration of some antipsychotics (in particular, clozapine, olanzapine and haloperidol). If available, use therapeutic drug monitoring to guide the lowest effective dose⁴ ⁵
address adverse effects that occur; see:

For information on antipsychotic poisoning, see here.

Table 1. Approximate relative frequency of common adverse effects of antipsychotics
Printable table

[NB1] [NB2] [NB3] [NB4]
amisulpride aripiprazole asenapine brexpiprazole cariprazine chlorpromazine clozapine flupentixol haloperidol lurasidone olanzapine paliperidone periciazine quetiapine risperidone ziprasidone zuclopenthixol
amisulprideStroup 2018 Vancampfort 2015 Huhn 2019
anticholinergic effects	–
cardiometabolic effects	+
extrapyramidal effects [NB5]	+
hyperprolactinaemia	+++
orthostatic hypotension [NB5]	– to +
sedation [NB5]	+
QT-interval prolongation Polcwiartek 2016 Stroup 2018 Huhn 2019	++ to +++
aripiprazoleLeucht 2017
anticholinergic effects	– to +
cardiometabolic effects	– to +
extrapyramidal effects [NB5]	+
hyperprolactinaemia	–
orthostatic hypotension [NB5]	+
sedation [NB5]	– to +
QT-interval prolongation Polcwiartek 2016 Stroup 2018 Huhn 2019	– to +
asenapine
anticholinergic effects	+
cardiometabolic effects	+
extrapyramidal effects [NB5]	+ to ++
hyperprolactinaemia	+
orthostatic hypotension [NB5]	+
sedation [NB5]	+
QT-interval prolongation Polcwiartek 2016 Huhn 2019	+
brexpiprazole
anticholinergic effects	– to +
cardiometabolic effects	– to +
extrapyramidal effects [NB5]	+
hyperprolactinaemia	–
orthostatic hypotension [NB5]	– to +
sedation [NB5]	– to +
QT-interval prolongation Huhn 2019	– to +
cariprazineSchnieider-Thoma [Leucht] 2022
anticholinergic effects	– to +
cardiometabolic effects	– to +
extrapyramidal effects [NB5]	+
hyperprolactinaemia	–
orthostatic hypotension [NB5]	– to +
sedation [NB5]	– to +
QT-interval prolongation Huhn 2019	– to +
chlorpromazine
anticholinergic effects	++
cardiometabolic effects	++ to +++
extrapyramidal effects [NB5]	++
hyperprolactinaemia	++
orthostatic hypotension [NB5]	++
sedation [NB5]	++ to +++
QT-interval prolongation Polcwiartek 2016 Stroup 2018	++
clozapine [NB6]
anticholinergic effects	+++
cardiometabolic effects	+++
extrapyramidal effects [NB5]	–
hyperprolactinaemia	–
orthostatic hypotension [NB5]	+++
sedation [NB5]	+++
QT-interval prolongation Polcwiartek 2016 Stroup 2018	+ to ++
flupentixol
anticholinergic effects	++
cardiometabolic effects	++
extrapyramidal effects [NB5]	++ to +++
hyperprolactinaemia	– to +
orthostatic hypotension [NB5]	+
sedation [NB5]	+
QT-interval prolongation Polcwiartek 2016	++
haloperidol
anticholinergic effects	+
cardiometabolic effects	+ to ++
extrapyramidal effects [NB5]	+++
hyperprolactinaemia	++
orthostatic hypotension [NB5]	+ to ++
sedation [NB5]	+
QT-interval prolongation Polcwiartek 2016 Stroup 2018 Huhn 2019	+++
lurasidone
anticholinergic effects	– to +
cardiometabolic effects	– to +
extrapyramidal effects [NB5]	+ to ++
hyperprolactinaemia	+
orthostatic hypotension [NB5]	– to +
sedation [NB5]	+
QT-interval prolongation Polcwiartek 2016 Stroup 2018 Huhn 2019	– to +
olanzapine
anticholinergic effects	++
cardiometabolic effects	+++
extrapyramidal effects [NB5]	– to +
hyperprolactinaemia	+
orthostatic hypotension [NB5]	+ to ++
sedation [NB5]	++
QT-interval prolongation Polcwiartek 2016 Stroup 2018 Huhn 2019	+ to ++
paliperidone
anticholinergic effects	+
cardiometabolic effects	++
extrapyramidal effects [NB5]	+
hyperprolactinaemia	+++
orthostatic hypotension [NB5]	+ to ++
sedation [NB5]	+
QT-interval prolongation Polcwiartek 2016 Stroup 2018 Huhn 2019	+
periciazine
anticholinergic effects	+++
cardiometabolic effects	++
extrapyramidal effects [NB5]	+
hyperprolactinaemia	+++
orthostatic hypotension [NB5]	++
sedation [NB5]	+++
QT-interval prolongation	limited or no data
quetiapine
anticholinergic effects	+++
cardiometabolic effects	++ to +++
extrapyramidal effects [NB5]	– to +
hyperprolactinaemia	– to +
orthostatic hypotension [NB5]	++
sedation [NB5]	++ to +++
QT-interval prolongation Polcwiartek 2016 Stroup 2018 Huhn 2019	+ to ++
risperidone
anticholinergic effects	+
cardiometabolic effects	++
extrapyramidal effects [NB5]	+
hyperprolactinaemia	+++
orthostatic hypotension [NB5]	+ to ++
sedation [NB5]	+
QT-interval prolongation Polcwiartek 2016 Stroup 2018 Huhn 2019	+ to ++
ziprasidone
anticholinergic effects	+
cardiometabolic effects	+
extrapyramidal effects [NB5]	+
hyperprolactinaemia	+
orthostatic hypotension [NB5]	+
sedation [NB5]	++
QT-interval prolongation Polcwiartek 2016 Stroup 2018 Huhn 2019	+++
zuclopenthixol
anticholinergic effects	++
cardiometabolic effects	++
extrapyramidal effects [NB5]	++ to +++
hyperprolactinaemia	+++
orthostatic hypotension [NB5]	+
sedation [NB5]	+++
QT-interval prolongation Polcwiartek 2016	limited or no data
Note: Approximate frequencies of adverse effects: – = negligible or absent; + = infrequent; ++ = moderately frequent; +++ = frequent NB1: The information in this table is based on a combination of reported adverse effect data and expert opinion; it is intended as a guide only and should be interpreted in the context of the patient (eg concurrent drugs, drug history, physical health, interindividual variation in pharmacokinetics). Adverse effects are similar with oral and long-acting injectable formulations, and are more likely with high doses. Consult a drug information resource for comprehensive information on antipsychotic adverse effects. NB2: A rare adverse effect of antipsychotics is neuroleptic malignant syndrome. NB3: Limited data suggest adverse effects may be more severe in children than in adults. NB4: This table lists the approximate relative frequency of adverse effects, not the intensity with which they occur. NB5: This adverse effect is generally more frequent when starting an antipsychotic or with a rapid dose increase, or starting or stopping an interacting drug. NB6: For additional information on clozapine adverse effects, see here.

¹ Many antipsychotics are metabolised by cytochrome P450 enzymes. Information on drug interactions mediated through these enzymes can be found at the University of Indiana School of Medicine's drug interaction website.Return

² For advice on a healthy diet, see Australian Dietary Guidelines.Return

³ For advice on physical activity, see Australia's Physical Activity and Sedentary Behaviour Guidelines and the Australian 24-Hour Movement Guidelines.Return

⁴ A list of Australian laboratory test databases is available at the Australasian Association for Clinical Biochemistry and Laboratory Medicine (AACB) 'Testing for health' website.Return

⁵ For information on therapeutic reference ranges of psychotropics, see Hiemke C, Bergemann N, Clement HW, Conca A, Deckert J, Domschke K, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry 2018;51(1-02):9-62. [URL]Return