Side Effects of Antipsychotic Medication (Short and Long-Term)

Schizophrenia is a serious and debilitating mental disorder. It is a heterogeneous disorder that can present with numerous symptoms. In general, the symptoms of the disorder can be divided into positive symptoms (excesses) that include hallucinations and delusions, and negative symptoms (deficits) that include a paucity of speech, a paucity of emotional expression, and a paucity of movement. Antipsychotic medications have been used to address primarily the positive symptoms of schizophrenia; however, newer antipsychotic medications have some effect on the negative symptoms. In addition, these medications are used to treat other disorders, including other psychotic disorders, the hallucinations that occur in psychotic depression, bipolar disorder with delirium, and hallucinations occurring as a result of drug abuse or overdose. They are even used to treat agitation in patients who have dementia or a hyperactive type of delirium.

There are numerous antipsychotic medications, and basically, the major effects of the antipsychotic medications are actually dependent on their order of development. Each generation of antipsychotic medications has a slightly different primary mechanism of action, and this produces both different therapeutic effects as well as different side effect profiles. Since a complete list of the side effect profile of every psychotic medication would be massive, it is useful to conceptualize the main side effects associated with the major developmental classes of antipsychotic medications.

 According to pharmaceutical manuals like The Manual of Clinical Psychopharmacology and Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, antipsychotic medications can be broken down into three categories.

Generations of Antipsychotics and Respective Side Effects

  • First-generation antipsychotics: The effects of medications were discovered by accident and include medications such as Haldol (haloperidol) and Thorazine (chlorpromazine). They are the earliest antipsychotic medications to be used in the treatment of schizophrenia and related disorders. Their primary mechanism of action was as a dopamine antagonist, meaning that the drug blocks the release, distribution, and effects of the neurotransmitter dopamine. However, as with all antipsychotic medications, other neurotransmitters are also affected but not to the same extent as the effects of the primary mechanism of action of the drug.First-generation antipsychotics have a high incidence of extrapyramidal side effects that are similar to the presentation of individuals who have Parkinson’s disease. In cases where the individual has used the medication for a significant length of time, these extrapyramidal side effects may become permanent, even after the drug has been discontinued.
    The side effects of these medications include:
    • Muscle rigidity
    • Bradykinesia (significantly slowed movements)
    • Dystonia (involuntary muscle movements and contractions)
    • Muscle tremor
    • Akathisia (significant restlessness and the feeling as if one needs to be in constant movement or motion)
    • Tardive dyskinesia (involuntary movements of the face, especially the mouth and lips, and arms and legs)
    • Neuroleptic malignant syndrome (a serious and often life-threatening condition that is characterized by muscle rigidity, fever, sweating, irregular heartbeat, blood pressure changes, and altered mental status, including confusion and disorientation)
  • Second-generation antipsychotics: This class of antipsychotics was developed to allow for the treatment of schizophrenia in an efficient manner and also to avoid the serious side effects associated with antipsychotic drugs. This group includes drugs such as Seroquel (quetiapine), Zyprexa (olanzapine), and Clozaril (clozapine). These drugs work on different dopamine receptors (first-generation antipsychotics primarily worked on the D2 dopamine receptor) and a few of them also have effects on the neurotransmitter serotonin.They have fewer extrapyramidal symptoms but may induce milder extrapyramidal symptoms. Typical side effects for this class of drugs include:
    • Issues with sedation
    • Dizziness
    • Weight gain
    • Sexual dysfunction
    • Cardiac effects
    • Hypotension
    • Dry mouth
    • Constipation
    • Some extrapyramidal side effects, which most often include rigidity, tremor, and akathisia
  • Third-generation antipsychotic medications (sometimes referred to as serotonin-dopamine activity monitors): The drugs in this class were developed to control for the side effects of the other classes of antipsychotic medications and still be effective in dealing with both positive and negative symptoms of schizophrenia. The best known of these drugs is Abilify (aripiprazole). These drugs affect the neurotransmitters serotonin, dopamine, and norepinephrine.The most common side effects of these drugs include:
    • Nausea
    • Vomiting
    • Headache
    • Insomnia
    • Constipation
    • Tremors

    Antipsychotic medications do not produce euphoria and are not significant drugs of abuse. Even with individuals who are prescribed them, they are rarely abused, except in cases where individuals may have serious cognitive issues that affect their judgment and may take too much of the medication. When individuals take more of antipsychotic medication than prescribed, the potential for the above side effects is significantly increased. In some cases, serious side effects, such as neuroleptic malignant syndrome or extrapyramidal side effects, are likely.

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