Which antipsychotics are less likely to disrupt thermal regulation?

Antipsychotics with Lower Risk of Thermal Dysregulation

Aripiprazole and quetiapine are the antipsychotics least likely to disrupt thermal regulation, with aripiprazole being the preferred option due to its minimal impact on thermoregulation.

Mechanism of Thermal Dysregulation with Antipsychotics

Antipsychotics can disrupt body temperature regulation through several mechanisms:

1. Hypothalamic interference - affecting the preoptic region that coordinates thermoregulation
2. Neurotransmitter effects:
   • Dopamine D2 receptor antagonism
   • Serotonin 5-HT2 receptor blockade
   • Alpha-1 adrenergic receptor blockade (causing peripheral vasodilation)
3. Reduction in shivering capability

Antipsychotics by Risk of Thermal Dysregulation

Lower Risk Options:

1. Aripiprazole:

   • Third-generation antipsychotic with partial dopamine agonist activity
   • Less likely to cause extrapyramidal symptoms (EPS) 1
   • Has minimal impact on thermal regulation due to its unique mechanism as a partial D2 agonist rather than pure antagonist
   • Recommended dosing: 5 mg PO daily, can be titrated as needed 1

2. Quetiapine:

   • Second-generation antipsychotic
   • Less likely to cause EPS than other atypical antipsychotics 1
   • FDA label specifically notes thermal regulation concerns but with appropriate monitoring can be safely used 2
   • Starting dose: 25 mg (immediate release) PO, typically given twice daily 1
   • May cause sedation and orthostatic hypotension

Moderate to Higher Risk Options:

1. Olanzapine:

   • Associated with cases of hypothermia, especially during initiation or dose increases 3
   • Starting dose: 2.5-5 mg PO or SC daily 1
   • May cause drowsiness and orthostatic hypotension

2. Risperidone:

   • Has been associated with hypothermia cases 4
   • Starting dose: 0.5 mg PO, can be given up to twice daily 1
   • Higher risk of EPS compared to other atypical antipsychotics 5

3. First-generation antipsychotics (haloperidol, chlorpromazine):

   • Highest risk for thermal dysregulation
   • Strong dopamine antagonism leads to greater risk of neuroleptic malignant syndrome (NMS)
   • Chlorpromazine has significant anticholinergic effects that further disrupt temperature regulation 1

Clinical Considerations

1. Monitoring recommendations:

   • Monitor body temperature closely during initiation and dose adjustments
   • Highest risk period is during the first few days after starting or increasing doses 3
   • Be particularly vigilant in elderly patients and those with pre-existing CNS disorders

2. Risk factors for thermal dysregulation:

   • Schizophrenia (higher risk than other conditions treated with antipsychotics) 3
   • Advanced age
   • Dehydration
   • Extreme environmental temperatures
   • Concomitant medications with anticholinergic effects

3. Warning signs:

   • Both hyperthermia (NMS) and hypothermia can occur
   • NMS presents with rigidity, altered mental status, autonomic instability, and fever
   • Hypothermia may present more insidiously and be missed if not specifically monitored

Practical Algorithm for Antipsychotic Selection Based on Thermal Regulation Concerns

1. First choice: Aripiprazole (lowest risk of thermal dysregulation)
2. Second choice: Quetiapine (low-moderate risk)
3. Third choice: Other atypical antipsychotics (olanzapine, risperidone)
4. Last resort: First-generation antipsychotics

Important Caveats

• Even "lower risk" antipsychotics can still cause thermal dysregulation in susceptible individuals
• The FDA label for quetiapine specifically warns that "disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents" 2
• Patients taking any antipsychotic should be advised to avoid conditions that may contribute to temperature dysregulation (extreme heat, dehydration, strenuous exercise) 2
• If a patient's clinical condition deteriorates after starting antipsychotic medication, always check body temperature 4