Bipolar Disorder Pharmacotherapy

Bipolar Disorder Pharmacotherapy

1. Definition, disease overview & goals of pharmacotherapy

• Bipolar disorder is a chronic mood (affective) disorder with cyclically alternating manic and depressive phases; the primary symptom is a change in mood state (KDT 8e Ch.32, p.462).
  • Mania — elated or irritable mood, reduced sleep, hyperactivity, uncontrollable thought and speech (flight of ideas, racing thoughts), high energy, sometimes reckless or violent behaviour and progressive loss of contact with reality (KDT 8e Ch.32, pp.462, 477).
  • Depression — sadness, loss of interest/pleasure, worthlessness, guilt, physical and mental slowing, melancholia, self-destructive ideation (KDT 8e Ch.32, p.462).
• Two major categories (KDT 8e Ch.32, p.463):
  • Bipolar I — manic episodes only, or both manic and depressive phases.
  • Bipolar II — cycles of hypomania alternating with major depression, but no full manic episodes.
• Mixed features — concurrent manic and depressive symptoms; cariprazine has specific data in mania with mixed features (Maudsley 14e Ch.2, p.302).
• Rapid cycling — frequent mood-episode recurrence; responds poorly to lithium, and valproate has only limited utility (Maudsley 14e Ch.2, p.290; KDT 8e Ch.32, p.478).
• Course & burden — individuals who experience mania have an 80–90% lifetime risk of subsequent manic episodes; patients with bipolar I and bipolar II spend 32% and 50% of their time, respectively, in a depressive phase (G&G 14e Ch.19, pp.377–8).
• Suicide burden — ~15% of people with bipolar disorder eventually die by suicide; this drives the central role of lithium (the mood stabiliser with the most robust anti-suicide data) (Maudsley 14e Ch.2, p.281; G&G 14e Ch.19, p.377).
• Pathophysiology (working models, not disease-specific) — dopaminergic overactivity in the limbic system is implicated in mania (as in schizophrenia); a transdiagnostic dopamine hypothesis underlies the anti-manic efficacy of dopamine-system drugs. Treatment remains empirical and symptom-oriented, not curative (KDT 8e Ch.32, pp.462–3; Maudsley 14e Ch.2, p.300).
• General goals of pharmacotherapy — (i) rapid control of acute mania; (ii) treatment of bipolar depression; (iii) maintenance/prophylaxis to prevent both manic and depressive relapse and reduce suicide; complete remission and prevention of both poles is the maintenance aim (Maudsley 14e Ch.2, pp.279–80).