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Side Effects of


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Description: Antipsychotics are used in the treatment of a number of disorders including psychosis in schizophrenia, bipolar disorder, and dementia-related psychosis in elderly patients. They are broadly split into two groups: typical antipsychotics and atypical antipsychotics.

So-called typical or “first generation” antipsychotics include:

  • Butyrophenones such as haloperidol
  • Diphenylbutylpiperidine such as pimozide
  • Phenothiazines such as chlorpromazine
  • Thioxanthenes such as flupentixol
  • Atypical or “second generation” antipsychotics include:

  • Amoxapine
  • Asenapine
  • Aripiprazole
  • Clozapine
  • Potentially Serious Side Effects and Black Box Warning

    Antipsychotics carry serious adverse effects, including potentially fatal cardiac arrest, difficulty breathing, suicidal ideation, and tardive dyskinesia, which is potentially disfiguring and marked by permanent uncontrollable movements of the mouth and facial muscles). (Journal of Clinical Psychiatry “Risk of cerebrovascular adverse events in older adults using antipsychotic agents: a propensity-matched retrospective cohort study,” Jun 2010); International Clinical Psychopharmacology “Risk excess of mortality and use of antipsychotics: a case-noncase study,” Jan 2017)

    The U.S. Food and Drug Administration has issued a black box warning on their use in the elderly due this population’s propensity toward serious and often fatal adverse reactions. (The Journal of the American Society of Consultant Pharmacists “The impact of FDA’s warning on the use of antipsychotics in clinical practice: a survey, Nov 2010).

    Side Effects of Typical Antipsychotics

    Butyrophenones like haloperidol (Haldol) are associated with the following side effects
    (La Clinica Terapeutica “Effectiveness of antipsychotics in schizophrenia and related disorders. Results of a naturalistic study,” April 2011):

  • Extrapyramidal disorder (issues with movement)
  • Hyperkinesia (increased movement)
  • Headache
  • Tardive dyskinesia (involuntary movement of the face and jaw)
  • Dystonia
  • Dyskinesia
  • Asathisa
  • Bradykinesia (decreased movement)
  • Insomnia
  • Agitation
  • Depression
  • Confusion
  • Constipation
  • Dry mouth
  • Nausea
  • Vomiting
  • Urinary retention
  • Erectile dysfunction
  • Hypotension (low blood pressure)
  • Rash
  • Muscle rigidity
  • Dyspnea (difficulty breathing)
  • Diphenylbutylpiperidines are associated with the following side effects (Proceedings of the National Academy of Sciences of the United States of America,”Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists,” Aug 2003):

  • Somnolence (lack of energy)
  • Dizziness
  • Extrapyramidal disorder
  • Headache
  • Lethargy
  • Tremor
  • Hyperkinesia
  • Asthenia
  • Extreme exhaustion
  • Hyperhidrosis (increased sweating)
  • Nocturia (increased nighttime urination)
  • Urinary frequency
  • Erectile dysfunction
  • Muscle rigidity
  • Myalgia (muscle pain)
  • Side Effects of Atypical Antipsychotics

    Atypical antipsychotics carry a large array of side effects. (Pharmacogenomics “Pharmacogenetics of second-generation antipsychotics,” Apr 2014). These include:

  • Drowsiness (14%)
  • Restlessness
  • Nervousness
  • Tremors
  • Confusion
  • Ataxia
  • Alterations in EEG patterns
  • Dizziness
  • Headache
  • Tingling
  • Paresthesia (pins and needles)
  • Tinnitus (ringing in ears)
  • Extrapyramidal symptoms (usually manifests as issues with movement like tardive dyskinesia and can be permanent)
  • Peculiar taste in mouth
  • Nausea
  • Constipation (12%)
  • Dry mouth (14)
  • Numbness
  • Blurred vision
  • Rash
  • Edema
  • Fatigue
  • Weakness
  • Increased sweating
  • Hypertension (high blood pressure)
  • Edema (swelling)
  • Weight gain
  • Increased appetite
  • Anemia (low red blood cell concentration)
  • Dysmenorrhea (painful menstruation)
  • Insomnia
  • Anxiety
  • Agitation
  • Depression
  • Irritability
  • Suicidal ideation
  • Anger
  • Muscle rigidity
  • Arthralgia (joint pain)
  • Somnolence (lack of energy)
  • Dizziness
  • Extrapyramidal signs (often present as motor problems)
  • Fatigue
  • Tremor
  • Headache
  • Akathisia (the compelling need to stay in constant motion)
  • Other less common side effects of atypical antipsychotics occuring in less than 1% of patients include (Journal of Psychosocial Nursing and Mental Health Services “Atypical antipsychotics are not all alike: side effects and risk assessment” (Sep 2014):

  • Neutropenia (low white blood cell)
  • Sexual dysfunction
  • Amenorrhea (no menstruation)
  • Syncope (fainting)
  • Orthostatic hypotension (low blood pressure when standing up)
  • Hypotension (low blood pressure)
  • Understand Your Risks with the Rxight® Genetic Test

    Some patients may not experience side effects when taking antipsychotics, while others are not as fortunate. This interpatient variability can be explained by the patients’ differing genetics.
    Identifying individual differences in medication metabolism is important for clinical decision making. For example, if a clinician knows a patient’s genetically modulated metabolism of medications, they can alter the dose given a patient’s known genetic variations or not prescribe the medication at all.

    Specifically, Rxight® DNA testing is based on the sequencing of 18 genes to establish how patients are likely to respond to hundreds of clinically relevant medications (including most antipsychotics). Each patient receives a Personalized Medication Review® interpreted by a pharmacist trained in pharmacogenetics – providing you and your prescriber with a “medication blueprint” for life.

    How Does Pharmacogenetic Testing Work?

    Some patients may not experience side effects when taking antipsychotics, while others may experience multiple severe side effects. This inter-patient variability can be partly explained by the patients’ differing genetics. (BMC Psychiatry “Effects of typical and atypical antipsychotic drugs on gene expression profiles in the liver of schizophrenia subjects,” Sep 2009). Polymorphisms (variants) in the genes that code for the enzymes and receptors that interact with antipsychotics could increase the probability of developing side effects when taking the drug.Patients with genes that cause them to be “poor metabolizers” do not process the medication quickly in their bodies, and thus are prone to serious adverse effects. Conversely, so-called “fast metabolizers” process the medication quickly, and thus may not derive therapeutic benefit.


    Contributors to this Article:
    Michael Sapko, MD, PhD; Deborah Kallick, PhD, Medicinal Chemistry

    Antipsychotics Tested Include:

    Read more about Rxight® Genetic Testing for Psychiatric Medications