Does haloperidol (antipsychotic medication) cause dysphoria as a side effect?

From the Guidelines

Haloperidol can cause dysphoria as a side effect, and this risk should be considered when prescribing this medication, especially at higher doses. Haloperidol is a first-generation (typical) antipsychotic medication that works primarily by blocking dopamine D2 receptors in the brain. This dopamine blockade, while effective for treating psychotic symptoms, can lead to unpleasant subjective experiences including dysphoria, which is characterized by feelings of unease, dissatisfaction, and general unhappiness. The dysphoric effects are thought to result from the medication's impact on the brain's reward pathways, which rely on dopamine signaling for normal function. Patients taking haloperidol may experience this side effect alongside other extrapyramidal symptoms like akathisia (restlessness) and akinesia (reduced movement), which can contribute to the overall dysphoric experience.

Some key points to consider when prescribing haloperidol include:

• The risk of dysphoria appears to be dose-dependent and may be more pronounced at higher doses 1
• Extrapyramidal side-effects from antipsychotic treatment should be avoided in order to encourage future adherence to medication 1
• Anticholinergics should not be used routinely for preventing extrapyramidal side effects, but short-term use may be considered only in individuals with significant extrapyramidal side effects when dose reduction and switching strategies have proven ineffective 1
• If a patient experiences dysphoria while taking haloperidol, their healthcare provider might consider dose adjustment, switching to a second-generation antipsychotic with less D2 receptor affinity, or adding medications to manage this side effect.

It's also important to note that the provided evidence does not directly address the question of haloperidol causing dysphoria, but it does provide information on the potential side effects of antipsychotic medications and the importance of considering these side effects when prescribing these medications. However, based on the general knowledge of haloperidol's mechanism of action and its potential side effects, it is reasonable to conclude that haloperidol can cause dysphoria as a side effect.

From the FDA Drug Label

Other CNS Effects Insomnia, restlessness, anxiety, euphoria, agitation, drowsiness, depression, lethargy, headache, confusion, vertigo, grand mal seizures, exacerbation of psychotic symptoms including hallucinations and catatonic-like behavioral states which may be responsive to drug withdrawal and/or treatment with anticholinergic drugs

The FDA drug label does mention dysphoria is not explicitly listed, but anxiety, depression, and restlessness are mentioned as possible side effects of haloperidol. However, dysphoria is not directly mentioned. Dysphoria is a state of unease or dissatisfaction, and while the label mentions related symptoms, it does not directly answer the question. Therefore, based on the information provided in the drug label, it is unclear if haloperidol causes dysphoria as a side effect 2 2.

From the Research

Haloperidol and Dysphoria

• Haloperidol has been associated with dysphoria as a side effect in some studies. For example, a study published in 1995 found that dysphoria occurred in about 40% of healthy volunteers given haloperidol 5 mg in two consecutive pharmacokinetic studies 3.
• The study also found that akathisia was only detected in 8% (first study) and 16% (second study) of the subjects, suggesting that dysphoria can occur independently of akathisia.
• Another study published in 2013 found that haloperidol caused a range of adverse effects, including movement disorders, but did not specifically mention dysphoria as a side effect 4.
• However, a study published in 2002 found that haloperidol was associated with a range of side effects, including extrapyramidal symptoms, but did not specifically mention dysphoria 5.
• It is worth noting that the evidence for haloperidol causing dysphoria is not consistent across all studies, and more research may be needed to fully understand the relationship between haloperidol and dysphoria.

Comparison with Other Antipsychotics

• Some studies have compared the side effects of haloperidol with other antipsychotics. For example, a study published in 2002 found that risperidone was associated with fewer extrapyramidal symptoms than haloperidol 5.
• Another study published in 2005 found that conventional antipsychotics, such as haloperidol, may be less efficacious at protecting against a switch to depression than atypical antipsychotics, divalproate or lithium 6.
• A study published in 2020 found that intravenous haloperidol was associated with a range of side effects, including extrapyramidal symptoms, but did not specifically mention dysphoria 7.

Clinical Implications

• The findings of these studies have implications for the clinical use of haloperidol. For example, clinicians may need to monitor patients for signs of dysphoria and other side effects when prescribing haloperidol.
• The choice of antipsychotic medication may depend on the individual patient's needs and medical history, as well as the potential risks and benefits of each medication.
• Further research is needed to fully understand the relationship between haloperidol and dysphoria, and to develop effective strategies for managing this side effect.