​​Antipsychotic drugs can cause a broad range of side effects. The risk varies with the type of antipsychotic (typical or atypical) and the individual drug. The side effects are common and contribute considerably to non-adherence to antipsychotic medication.

Extrapyramidal side effects (EPS)


EPS occurs as a result of blockade of the dopamine receptors in the basal ganglia (nigrostriatal pathway). The magnitude depends on the affinity of the antipsychotic drugs for D2 receptors in the striatum. EPS are frequently with typical antipsychotic drugs and less commonly with atypical agents. Atypical drugs such as paliperidone, amisulpride and risperidone, can cause EPS, particularly at high doses.cpcd There are four types of EPS which consist of:



•  Acute dystonias consist of torticollis (involuntary spasm of the muscles in the neck, which consequently turns the head to the side), protrusion of the tongue, oculogyric crisis (rotating eyeballs), grimacing. These symptoms commonly occur within 72 hours of starting an antipsychotic. They often decline with time, and are reversible on withdrawal of drug treatment.
•   Akathesia can be portrayed as restlessness. This typically occurs within the first two weeks of the initiation of an antipsychotic drug. Additionally, it can present several months later following a rapid increase in dose.
•  Parkinsonism- This commonly occurs within a month of initial antipsychotic treatment. It is characterised by akinesia (involuntary muscle movement), lack of facial expression, course tremors and stiffness.
   
•   Tardive dyskinesia: This is a fatal movement disorder of late onset which can occur with prolonged exposure to antipsychotics. It is characterised by a range of rhythmic involuntary movements that typically affect the muscles of the limbs, trunk or face. This usually includes tongue protrusion, lip smacking, tapping of the foot or an abnormal posture. Tardive dyskinesia can be irreversible and may worsen on withdrawal of the antipsychotic drug, it is also usually resistant to drug therapy.
   

Hyperprolactinaemia


The tuberohypophyseal pathway controls dopamine release. Dopamine inhibits the secretion of prolactin via D2- receptors. The antagonist action of antipsychotic drugs at D2-receptors can consequently raise the plasma concentration of prolactin.

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Hyperprolactinaemia is a common side effect of the typical antipsychotics. It also occurs with the use of atypical antipsychotic drugs (it is common with amisulpride and risperidone and less common or absent with aripiprazole, olanzapine, quetiapine and clozapine).

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Hyperprolactinaemia can be asymptomatic in some individuals, even with significantly raised prolactin levels. On the other hand, in some patients, hyperprolactinaemia can result in a reduction in bone mineral density, sexual dysfunction, breast enlargement (gynaecomastia) and galactorrhoea. In addition it can also cause menstrual disturbances in women.

Neuroleptic malignant syndrome


Neuroleptic malignant syndrome (NMS) is a rare but potentially serious disorder, which is associated with the antagonistic action of antipsychotic drugs. It has been suggested that NMS, occurs as a result of rapid blockade of dopamine receptors in the temperature regulatory regions, located in the corpus striatum and hypothalamus.

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NMS is characterised by hyperthermia, muscle rigidity and fluctuating levels of consciousness. Antipsychotic therapy should be immediately discontinued and medical attention should be sought. Death due to NMS has been known to occur in 10 per cent of cases. Those patients that have been prescribed a new potent dopamine antagonist, that present with physical exhaustion or seem dehydrated are prone to the development of NMS.

Weight gain


All antipsychotic drugs frequently cause weight gain; however, it is more common with atypical antipsychotic agents. Olanzapine and clozapine have the greatest potential to cause weight gain. Weight gain may possibly be a result of histamine (H1) receptor blockade, which consequently increases appetite via the hypothalamic eating centres. The use of olanzapine has been related to a 3.5 to 4kg weight gain, which can be seen in the first 10 weeks of treatment. In addition, weight gain can also increase the risk of type 2 diabetes in these individuals.

Impaired glucose tolerance


Hyperglycaemia and sometimes diabetes have been associated with typical and atypical antipsychotic drugs. This is significant with olanzapine, clozapine, risperidone and quetiapine.

Cardiovascular effects


Cardiovascular side effects such as arrythimias, hypotension and tachycardia can result antipsychotic treatment. QT-interval prolongation is associated with antipsychotic therapy, especially with haloperidol and pimozide. The QT interval represents the time it takes to complete the depolarisation and repolarisaton cycle of the ventricles. It increases the risk of torsades de pointes which is a potentially fatal arrhythmia and sudden cardiac death.

Hypotension


Clozapine, quetiapine and chlorpromazine can result in postural hypotension. This can especially occur during initial titration of dose.

Dyslipidaemia


Antipsychotic drugs vary in their ability to cause dyslipidaemia. Phenothiazines, olanzapine, clozapine, risperidone and quetiapine have been known to increase lipid levels, whereas drugs such as haloperidol and aripiprazole appear to have no effect on lipids.

Sexual dysfunction

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One of the major causes of non-adherence to antipsychotic treatment is sexual dysfunction. This can be due to several mechanisms.Reduced dopamine transmission and hyperprolactinaemia decrease libido; antimuscarinic effects can cause disorders of arousal; and alpha1-adrenoceptor antagonists are associated with erection and ejaculation problems in men. Risperidone and haloperidol commonly cause sexual dysfunction. If sexual dysfunction is thought to be antipsychotic-induced, dose reduction or switching medication should be considered.

Other side effects associated with antipsychotic drugs include sedation, antimuscarinic symptoms (such as dry mouth, blurred vision, constipation, urinary retention) and reduced seizure threshold.