What is the difference between an antipsychotic and a mood stabilizer?

Difference Between Antipsychotics and Mood Stabilizers

Antipsychotics and mood stabilizers are distinct medication classes with different primary mechanisms and indications, though some antipsychotics demonstrate mood-stabilizing properties and are now used interchangeably with traditional mood stabilizers in bipolar disorder treatment.

Primary Mechanisms of Action

Antipsychotics

• Antipsychotics exert their effect primarily as CNS dopamine receptor antagonists, blocking postsynaptic D2 receptors 1
• Second-generation "atypical" antipsychotics function as both serotonin-dopamine receptor antagonists, which accounts for their broader therapeutic effects 1
• Aripiprazole represents a "third-generation" antipsychotic with partial dopamine receptor agonist activity, distinguishing it mechanistically from other antipsychotics 1

Traditional Mood Stabilizers

• Lithium and valproate are the prototypical mood stabilizers, though their exact mechanisms differ from antipsychotics 2
• Lithium may work through central serotonin-enhancing properties and modulation of physiological stress reactions 3
• Valproate and other anticonvulsant mood stabilizers have distinct mechanisms unrelated to dopamine blockade 3

Clinical Indications and Efficacy Profiles

Traditional Distinctions

• Conventional antipsychotics (haloperidol, chlorpromazine) are effective antimanic agents but do not treat comorbid depressive symptoms, limiting their utility as true mood stabilizers 2
• Traditional mood stabilizers like lithium are effective across all phases of bipolar disorder—acute mania, acute depression, and maintenance therapy 3

Blurred Lines with Atypical Antipsychotics

• Recent evidence demonstrates that atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole) have mood-stabilizing effects with efficacy in acute mania and long-term relapse prevention 2, 4
• The American Academy of Child and Adolescent Psychiatry now recommends atypical antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) as first-line options alongside lithium and valproate for acute mania 3
• Olanzapine demonstrates efficacy across all phases of bipolar disorder without provoking manic or depressive symptomatology, meeting functional criteria for a mood stabilizer 5

Spectrum of Therapeutic Effects

Antimanic Efficacy

• Both antipsychotics and traditional mood stabilizers effectively treat acute mania 3, 2
• Atypical antipsychotics may provide more rapid symptom control than mood stabilizers alone, though both are considered first-line 3
• Combination therapy (mood stabilizer plus atypical antipsychotic) shows superior efficacy compared to either class alone for severe presentations 3, 6

Antidepressant Properties

• Traditional antipsychotics lack efficacy for depressive symptoms 2
• Certain atypical antipsychotics (particularly quetiapine and the olanzapine-fluoxetine combination) demonstrate intrinsic antidepressant properties 5
• Lamotrigine (a mood stabilizer) is particularly effective for preventing depressive episodes in maintenance therapy 3

Maintenance and Prophylaxis

• Lithium demonstrates superior evidence for long-term prevention of both manic and depressive episodes, with additional anti-suicide effects (reducing suicide attempts 8.6-fold and completed suicides 9-fold) 3
• Multiple atypical antipsychotics (aripiprazole, olanzapine, quetiapine) show prophylactic efficacy against mood episode recurrence comparable to traditional mood stabilizers 4
• Olanzapine's prophylactic efficacy against manic relapses may be superior to lithium 5

Side Effect Profiles

Antipsychotic-Specific Concerns

• Typical antipsychotics carry high risk of extrapyramidal symptoms and tardive dyskinesia (50% risk after 2 years of continuous use in young patients) 3
• Atypical antipsychotics have more favorable extrapyramidal side effect profiles but carry significant metabolic risks including weight gain, diabetes, and dyslipidemia 3, 6
• The American Academy of Child and Adolescent Psychiatry recommends monitoring BMI monthly for 3 months then quarterly, plus blood pressure, fasting glucose, and lipids at 3 months then yearly for patients on atypical antipsychotics 3

Mood Stabilizer-Specific Concerns

• Lithium requires monitoring of serum levels, renal function, and thyroid function every 3-6 months 3
• Valproate requires monitoring of hepatic function and hematological indices, and is associated with polycystic ovary disease in females 3
• Both lithium and valproate cause weight gain, but lithium is NOT associated with significant sedation, whereas valproate causes notable sedation 3

Current Clinical Practice Integration

Guideline Recommendations

• The American Academy of Child and Adolescent Psychiatry recommends lithium, valproate, or atypical antipsychotics as equivalent first-line options for acute mania/mixed episodes 3
• For maintenance therapy, lithium or valproate are suggested, with lithium showing superior long-term evidence 3
• Combination therapy with a traditional mood stabilizer plus an atypical antipsychotic is recommended for severe presentations and treatment-resistant cases 3

Practical Algorithm

• When choosing between classes, consider the phase of illness: acute mania favors either class or combination; bipolar depression favors quetiapine, olanzapine-fluoxetine, or lamotrigine; maintenance favors lithium or combination therapy 3
• Metabolic concerns favor lithium or aripiprazole over olanzapine, quetiapine, or clozapine 3
• Sedation concerns favor lithium over valproate or sedating antipsychotics 3
• Psychotic features favor antipsychotics (particularly aripiprazole, risperidone, or olanzapine) over mood stabilizers alone 3

Common Pitfalls

• Avoid using typical antipsychotics as first-line alternatives due to inferior tolerability and higher extrapyramidal symptom risk 3
• Do not assume all antipsychotics lack mood-stabilizing properties—atypical antipsychotics have demonstrated efficacy across all phases of bipolar disorder 2, 5, 4
• Failure to monitor for metabolic side effects of atypical antipsychotics is a critical oversight, as these medications carry significant cardiometabolic risks 3
• Recognize that the term "mood stabilizer" now functionally includes certain atypical antipsychotics based on their clinical efficacy profile, not just their original classification 5