Quetiapine

Quetiapine has a dose-dependent pharmacological profile. At lower doses, dopamine D2 receptor binding is brief and easily reversible, which explains why quetiapine produces very low rates of extrapyramidal side effects and prolactin elevation, even when used for sedation or insomnia (38).

Movement and Prolactin Effects

Quetiapine is among the least likely atypical antipsychotics to cause Parkinson’s-like side effects, including dystonia or akathisia (35, 36, 38). It also has minimal impact on prolactin levels, reducing the risk of sexual dysfunction, infertility, and prolactin-associated breast effects in both men and women (38).

Sedation and Cognitive Effects

Compared with first-generation antipsychotics, quetiapine is associated with a lower incidence of subjective negative experiences such as emotional blunting, anxiety, irritability, reduced motivation, and distress. These symptoms are a major cause of poor adherence with older antipsychotic medicines (35, 36).

Metabolic Effects

Quetiapine is unusual among antipsychotics in that it has documented misuse potential. Its calming and anxiolytic properties have led to non-medical use to enhance or offset the effects of other substances or to manage withdrawal symptoms (39). Increasing evidence suggests that repeated misuse may lead to psychological dependence, and overdose can be associated with significant toxicity (39).

Older Adults

Older adults are particularly sensitive to quetiapine’s side-effect profile (37, 38). Postural hypotension can lead to dizziness and falls, sometimes resulting in fractures. Cognitive effects such as confusion or memory impairment may be more pronounced and harder to distinguish from age-related cognitive decline. Metabolic effects, including weight gain, hyperglycaemia, and dyslipidaemia, are also clinically important in this group because of baseline cardiovascular risk.

Misuse and Toxicity

In cases of overdose or misuse, quetiapine can cause life-threatening toxicity, including severe hypotension, cardiac arrhythmias, marked sedation, and Parkinson’s-like symptoms (39).

Quetiapine Side Effects

Although quetiapine has a more favourable neurological side-effect profile than first-generation antipsychotics, it is associated with metabolic and sedative effects (35,37). 

Common side effects include

Weight gain, increases in blood glucose and cholesterol, dizziness, sedation, and cognitive slowing. Older adults are particularly vulnerable to balance problems, confusion, and orthostatic hypotension.

There are currently no formal CPIC guidelines for quetiapine dosing based on genetic profile. This reflects limited evidence rather than absence of metabolic relevance. Variability in CYP3A4 and CYP2D6 activity, combined with age, formulation, diet, and drug interactions, contributes to the wide range of individual responses observed in clinical practice.

What This Means for You

Older adults should be especially vigilant for dizziness, balance problems, and cognitive changes. Adequate hydration, slow position changes, and regular review of dose and formulation are important. Abrupt dietary changes, particularly with extended-release formulations, should be avoided. If quetiapine becomes less effective over time or increasingly relied upon for calming effects, this should be discussed with a clinician.

Quetiapine is widely used and effective when carefully monitored. Open communication with healthcare professionals is essential to maximise benefit and minimise risk.

Related Medications:

Other antipsychotic medicines include:

• Clozapine
• Aripiprazole
• Olanzapine
• Haloperidol
• Perphenazine
• Thioridazine
• Zuclopentixol