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Antipsychotics, or neuroleptics, are used to control the symptoms of psychotic disorders.

Want to treat both positive and negative symptoms; the positives are much easier to treat.


Second generation antipsychotics are serotonin-dopamine antagonists, blocking serotonin type 2 and D2 dopamine receptors. Their properties, including apparent specificity for the mesolimbic dopamine system, lead to improved tolerability as compared with older generation antipsychotics.





Antipsychotics are used for a number of conditions.


They are also often used in combination:

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Mechanisms of Action

Antipsychotics all inhibit dopamine systems in the brain. These include mesolimbic/mesocortical: associated with thought disorders; nigrostriatal, and tuberoinfundibular.


SDAs are alike in their low D2 receptor blockades, reduced risk of extrapyramidal side effects, decreased risk for tardive dyskinesia, and clear benefit for schizophrenia and acute mania. They differ in regards to chemical structure, receptor affinity, and side effect profile.


A new class of drug is the partial dopamine D2 agonists. These include apiprazole and paliperidone, the latter the metabolite of risperidone. These compete for endogenous dopamine at their receptors, leading to a functional reduction in activity.

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Classes and Members


novel/atypical antipsychotics

Risperidone is effective in once-daily dosing. Side effects include:


Olanzepine has the best discontinuation rate, but is one of the most frequent causes of weight gain.

Higher doses (above 20 mg/day) causes increased risk of EPSE.



Quetiapine (Seroquel) is not associated with EPSE.

Side effects include:

Doses can be achieved rapidly.

It can be used for insomnia as well.


Ziprazadone use has led to concerns surrounding QT inteveral prolongation.



Clozapine is the most effective treatment for treatment-resistant schizophrenia, as well as severe tardive dyskinesia.

Side effects include:





biological effects

predominant side effects

high potency

  • haldol
  • haloperidol
  • primarily dopaminergic; block D2 receptors
  • improve positive symptoms, but with no effect on negative symptoms
  • associated with extrapyramydial symptoms

medium potency

  • loxapine

low potency

  • methotrimeprazine

atypical antipsychotics

  • olanzapine (Zyprexa)
  • quetiapine (Seroquel)
  • clozapine (Clozaril)
  • ziprasidone (Geodon)
  • risperidone (Risperidol)
  • both dopaminergic (D1/D2) and seratonergic blockades, with higher affinity for 5-HT2
  • also the fast-off hypothesis: low affinity for, and fast dissociation from D2 receptor

less cognitive side effects

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Clinical Usage

Any SDA, save clozapine, may be considered for psychotic episodes. They usually require 4-6 weeks to reach full effectiveness. Start with low doses and gradually titrate upwards to reach desired dose.

For initial aggression or anxiety, lorazepam 1-2 mg may be used for symptom control.

If a person does not respond to a first SDA, a second may be attempted


At a high enough dose, massive sedation will occur

We seem to need 60-80% of D2 receptor blockade within the nigrostriatal tract, which is a surrogate marker for desired effects.

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Adverse Drug Reactions

There are some very bad side effects that accompany anti-psychotics, and adherence to agreed treatment is of serious concern. Perhaps 75% of patients stop treatment over 18 months. Injectible depots can be used to force compliance.


receptor type

adverse effects

dopamine D2

EPS, prolactin elevation (galactorrhea, amenorrhea, gynecomastia)


orthostatic hypotension, sexual dysfunction

muscarinic (M1)

urinary retention, constipation, blurred vision, dry mouth, tachycardia


sedation, weight gain


High potency drugs cause higher EPS side effects hyperprolactinemia and lower anticholinergic cardiovascular side






long term

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Resources and References

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