Side Effects of Atypical Antipsychotics

antipsychotics

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Atypical (a.k.a., “second-generation”) antipsychotics are commonly used in the treatment of psychotic disorders, and mood disorders as well. Compared to typical (first-generation) antipsychotics, the atypical antipsychotics have lower affinity for dopamine D2 receptors, and they also act at serotonin (5-HT) receptors (they are antagonists for these receptors). Other neurotransmitter receptors are affected as well, and each atypical antipsychotic preferentially antagonizes different receptors.

When atypical antipsychotics were first introduced, it was hoped that they would be more effective than typical antipsychotics and have fewer extrapyramidal side effects (see below). While these expectations may have been somewhat overblown and atypicals are not markedly superior in decreasing psychosis symptoms, most atypicals certainly have a lower risk of developing extrapyramidal side effects. However, they do come with their own array of side effects.

Extrapyramidal side effects (EPSE): These are movement-related side effects caused by dopamine antagonism. These include acute dystonia (torticollis, an uncomfortable muscular spasm of the neck; as well as spasms of the eyes, tongue, jaw), akathisia (motor restlessness and a need to remain in motion), tardive dyskinesia (repetitive, involuntary movements usually involving facial muscles), parkinsonian symptoms (resting tremor, rigidity, slowed movements), and neuroleptic malignant syndrome (potentially fatal!).
Elevated prolactin (PRL): This can lead to gynecomastia (breast growth) and galactorrhea (milk-production), which can be very distressing for male patients! Can also cause infertility and sexual dysfunction. It also happens with typical antipsychotics.
Weight gain: This can be very a troublesome symptom, and may lead to diabetes in some patients.
Sedation: This may prevent patients from engaging in their usual activities and work.
Orthostatic hypotension: Drop in blood pressure after standing from sitting position.

Some antipsychotics have especially severe side effects. Clozapine, for example, is extremely effective in treating psychosis but can lead to fatal agranulocytosis (drop in white blood cells), as well as tremendous weight gain and sedation. Ziprasidone use can lead to QTc prolongation and increase the risk for serious cardiac arrhythmia.

The above chart shows the relative side effect profiles of eight atypical antipsychotics (aripiprazole, clozapine, lurasidone, olanzepine, paliperidone, quetiapine, risperidone, ziprasidon) versus two typical antipsychotics (chlorpromazine, haloperidone).

  • Haddad PM, Sharma SG. 2007. Adverse effects of atypical antipsychotics: Differential risk and clinical  implications. CNS drugs; 21:911.
  • Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lassig B, Salanti G, Davis JM. 2013. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: A multiple treatments meta-analysis. Lancet; 382:951.
  • Meltzer HY. 2013. Update on typical and atypical antipsychotic drugs. Annual Review of Medicine: 64:393.
  • Sadock BJ, Sadock VA (Eds.). 2007. Serotonin-dopamine antagonists: Atypical antipsychotics. In: Kaplan & Sadock’s Synopsis of Psychiatry. Lippincott Williams & Wilkins, Philadelphia PA.
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