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Last updated: December 5, 2019


Antipsychotics are a heterogeneous group of substances used primarily to treat schizophrenia, psychosis, mania, delusions, and states of agitation. The term neuroleptics was formerly used interchangeably with antipsychotics because early antipsychotic drugs induced apathy, quiescence, and reduced psychomotor activity, but newer antipsychotic drugs no longer have these effects. The antipsychotic effect of first-generation (typical) antipsychotics (e.g., haloperidol) is based on D2 antagonism, while second-generation (atypical) antipsychotics interact with several receptors (e.g., D2, D3, D4, 5-HT). Extrapyramidal symptoms, which include acute dystonia, akathisia, and tardive dyskinesia, are the most common side effects of first-generation antipsychotics. Metabolic side effects (e.g., weight gain, insulin resistance), on the other hand, are more typical of second-generation antipsychotics. A potentially life-threatening side effect of both first-generation and second-generation antipsychotics is neuroleptic malignant syndrome, which manifests with fever, muscle rigidity, autonomic instability, and mental status changes.


Mechanism of action Indications Side effects
First-generation antipsychotics (FGAs) High-potency antipsychotics
  • Haloperidol
  • Fluphenazine
  • Perphenazine
  • Trifluoperazine
  • Pimozide
Low-potency antipsychotics
  • Chlorpromazine
  • Thioridazine
  • Promethazine
Second-generation antipsychotics (SGAs)
  • Clozapine
  • Olanzapine
  • Risperidone
  • Quetiapine
  • Amisulpride
  • Ziprasidone
  • Aripiprazole
  • Lurasidone
  • Asenapine
  • Iloperidone
  • Paliperidone


Adverse effects

Details First-generation antipsychotics Second-generation antipsychotics
Extrapyramidal symptoms (EPS)
  • See EPS below for details.
  • Significantly fewer motor side effects (EPS) due to reduced D2 receptor antagonism; greater affinity for 5HT2A receptors and interaction with other receptors
  • All FGAs cause elevated prolactin levels.
  • Annual monitoring of symptoms is recommended.
Prolonged QT interval
Anticholinergic effects
Metabolic effects
Sympatholytic effect
  • Common during treatment initiation and dose adjustments
  • Particularly olanzapine
  • All SGAs (tolerance usually develops within a few days of treatment)
  • Quetiapine is often used as a sleep aid in low doses.
  • Extremely rare
Other cardiac side effects
  • Not reported
Ocular effects
  • Not reported
  • Associated with phenothiazines (e.g., fluphenazine)
  • Patients receiving these medications should avoid extreme temperatures. [3]
Neuroleptic malignant syndrome
  • Life-threatening side effect
  • See NMS below for details.
  • All antipsychotics

Extrapyramidal symptoms (EPS)

EPS subtype Onset Symptoms Treatment

Acute dystonia (also see dystonia)

Hours to days
Pseudoparkinsonism Week 1
Akathisia Weeks 1–8
  • Restlessness/compelling urge to move
  • Inability to sit or stand still
Tardive dyskinesia Months–years
  • Involuntary movements of the mouth and tongue; limbs, face, and respiratory muscles caused by chronic use of antipsychotic drugs
    • Repetitive chewing and lip smacking
    • Choreic movements
  • Discontinuation of antipsychotic drug
    • Switch to SGA (less EPS)
    • Anticholinergics or antipsychotic dose reduction may initially worsen the condition.
  • Treatment: valbenazine and tetrabenazine [4]

Neuroleptic malignant syndrome (NMS) [5]

To remember the different symptoms of neuroleptic malignant syndrome, think "FALTER": Fever, Autonomic instability, Leukocytosis, Tremor, Elevated enzymes (creatine kinase, transaminases), Rigor


We list the most important adverse effects. The selection is not exhaustive.


  • All antipsychotics, with the exception of clozapine (used for treatment-resistant schizophrenia), have similar clinical effectiveness.
  • The choice of drug depends on the side effect profile of the antipsychotic drugs and the patient's clinical status.
  • SGAs are preferred in many cases because they carry a lower risk of EPS; however, in some patients (e.g., those with significant metabolic risk factors), FGAs may be more suitable.
Important indications Preferred agents
Acute therapy
  • High-potency antipsychotics (alternatively, low-potency antipsychotics)
Long-term therapy
  • SGAs
  • In cases of treatment failure, switch to high-potency antipsychotics (primarily effective for positive symptoms).
  • Tiapride

To reduce/avoid anticholinergic side effects in patients of advanced age, high-potency substances (e.g., haloperidol, risperidone) or melperone are preferred!


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  2. Jibson MD, Marder S, Hermann R. Second-Generation Antipsychotic Medications: Pharmacology, Administration, and Side Effects. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/second-generation-antipsychotic-medications-pharmacology-administration-and-side-effects.Last updated: May 15, 2017. Accessed: June 5, 2017.
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  9. Kowalski JM, Tarabar A. Medication-Induced Dystonic Reactions. Medication-Induced Dystonic Reactions. New York, NY: WebMD. http://emedicine.medscape.com/article/814632-overview. Updated: June 29, 2016. Accessed: May 18, 2017.
  10. Life in the fast lane - Acute Dystonic Reaction (Stiff and Twisted). https://lifeinthefastlane.com/toxicology-conundrum-030/. Updated: April 20, 2010. Accessed: May 18, 2017.
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