Chapter 39: Depression & Bipolar Disorder – Pharmacotherapy

Depression & Bipolar Disorder – Pharmacotherapy outlines the diagnosis, pathophysiology, and management of Major Depressive Disorder (MDD) and Bipolar Disorders. MDD is characterized by persistent alterations in behavior, cognition, and physical functioning, encompassing symptoms like depressed mood, loss of interest (anhedonia), sleep disturbances, and suicidal ideation. The illness is multifactorial, stemming from interactions among genetic, social, and physiological factors, with core neurochemical theories positing functional or absolute deficiencies in monoamines like serotonin, norepinephrine, and dopamine. Diagnosis of a major depressive episode requires meeting at least five specific criteria from the DSM-5 over a two-week period, including either depressed mood or anhedonia. Severity assessment often uses clinician-rated scales such as the HAM-D. Treatment goals prioritize achieving full remission, which is considered the only acceptable therapeutic outcome, replacing the previous goal of mere response (50% symptom reduction). Therapy is organized into acute, continuation, and maintenance phases, with maintenance lasting indefinitely for high-risk patients (e.g., three or more prior episodes). Nonpharmacologic options include various psychotherapies, such as Cognitive-Behavioral Therapy (CBT) and Interpersonal Therapy (IPT), while Electroconvulsive Therapy (ECT) is reserved for severe or refractory cases. Pharmacologic treatment generally starts with Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin Norepinephrine Reuptake Inhibitors (SNRIs), which are favored for their safety, tolerability, and reduced lethality in overdose compared to older agents. Antidepressants universally increase the availability of neurotransmitters in the synapse, either by inhibiting reuptake or metabolic breakdown. Side effect profiles drive agent selection, as all classes possess relatively equal efficacy. For example, SSRIs are noted for causing sexual dysfunction and gastrointestinal upset, while SNRIs risk dose-related adverse effects like treatment-emergent hypertension. Older Trcylicic Antidepressants (TCAs) are relegated to later lines of therapy due to their anticholinergic activity and significant cardiac conduction risks, and Monoamine Oxidase Inhibitors (MAOIs) require strict dietary adherence to avoid fatal hypertensive crises. Atypical agents, such as bupropion (which is often weight-neutral and lacks serotonergic sexual side effects) and mirtazapine (used for sedation and appetite stimulation), offer tailored alternatives. New multimodal drugs like vilazodone and vortioxetine act on multiple serotonin receptors and may offer faster onset or lower sexual side effect risk. Treatment failure is common, requiring strategies like dose optimization, augmentation (e.g., with bupropion or atypical antipsychotics), or switching medication classes. Special attention must be given to populations like adolescents (due to the FDA black box warning regarding increased suicide risk for those under age 25 taking SSRIs) and geriatrics (who are more sensitive to anticholinergic effects and hypotension). The chapter also addresses Bipolar Disorder, categorized into Bipolar I, Bipolar II, and Cyclothymic disorders, which is managed primarily with a combination of mood stabilizers (e.g., lithium, valproate) and atypical antipsychotics. Finally, the use of complementary agents like St. John’s wort is discouraged due to inconsistent efficacy and severe interaction risk, especially serotonin syndrome.