# Lecture 2: Mood Disorders ## Unit 2.6: Psychiatry --- ## Learning Objectives By the end of this lecture, students will be able to: 1. Apply DSM-5 diagnostic criteria for major depressive disorder using the SIG E CAPS mnemonic and identify clinical specifiers 2. Explain the neurobiology of depression including the monoamine hypothesis, neuroplasticity theory, and HPA axis dysregulation 3. Compare mechanisms of action and clinical applications of major antidepressant classes including SSRIs, SNRIs, and atypical agents 4. Differentiate bipolar I disorder, bipolar II disorder, and cyclothymic disorder based on episode criteria and clinical course 5. Describe the pharmacological management of mania and bipolar depression including mood stabilizers and atypical antipsychotics 6. Explain evidence-based psychotherapy approaches and special considerations for mood disorders in pregnancy and other populations --- ## Lecture Outline ### I. Major Depressive Disorder Major depressive disorder (MDD) represents one of the leading causes of disability worldwide, affecting approximately 17% of the population over a lifetime. Understanding its diagnostic criteria, clinical presentation, and evidence-based treatment is essential for all physicians. Epidemiology reveals important patterns. Lifetime prevalence approaches 17%, with women affected twice as frequently as men. Age of onset varies widely but peaks in the 20s. The disorder is highly recurrent—more than 50% of individuals who experience one episode will have another, and the risk increases with each subsequent episode. Comorbidity is the rule rather than exception: anxiety disorders, substance use, and medical conditions frequently co-occur. DSM-5 diagnostic criteria require five or more symptoms present during the same two-week period, representing a change from previous functioning, with at least one symptom being either depressed mood or anhedonia. The mnemonic SIG E CAPS captures the symptom criteria: Sleep changes (insomnia or hypersomnia), Interest decreased (anhedonia—loss of pleasure in previously enjoyable activities), Guilt or feelings of worthlessness (excessive or inappropriate), Energy decreased (fatigue nearly every day), Concentration impaired (difficulty thinking or indecisiveness), Appetite changes (decrease or increase with weight change), Psychomotor changes (agitation or retardation observable by others), and Suicidal ideation (thoughts of death, suicidal ideation, or suicide attempt). Depressed mood present most of the day, nearly every day, represents the core symptom. The diagnosis requires that symptoms cause clinically significant distress or functional impairment and are not attributable to substance use or medical conditions. Specifiers provide additional clinical information. Anxious distress indicates prominent anxiety symptoms including tension, restlessness, and fear of losing control. Melancholic features describe a severe subtype with profound anhedonia, depression worse in morning, early morning awakening, and psychomotor changes. Atypical features are characterized by mood reactivity (mood brightens in response to positive events), hypersomnia, hyperphagia with weight gain, and leaden paralysis (heavy, leaden feelings in limbs). Psychotic features indicate the presence of delusions or hallucinations. Peripartum onset specifies episodes during pregnancy or within four weeks postpartum. Seasonal pattern describes recurrent episodes with regular temporal relationship to seasons, typically winter onset with remission in spring. Panel A presents the SIG E CAPS mnemonic with each symptom illustrated and defined. Panel B displays MDD severity levels (mild, moderate, severe) with corresponding symptom count and functional impairment criteria. Panel C illustrates clinical specifiers including melancholic, atypical, and psychotic subtypes with their distinguishing features. Panel D shows the chronicity and recurrence pattern of MDD with statistics on relapse risk. --- ### II. Neurobiology of Depression Understanding depression's neurobiological underpinnings informs treatment selection and explains therapeutic mechanisms. Multiple theories contribute to our current understanding. The monoamine hypothesis, the oldest neurobiological theory, proposes that depression results from deficiency in monoamine neurotransmitters—serotonin, norepinephrine, and dopamine. Evidence supporting this hypothesis includes the observation that medications increasing monoamine availability improve depressive symptoms, while monoamine-depleting agents can induce depression. However, the hypothesis has significant limitations: antidepressants increase monoamine levels within hours, yet clinical improvement requires weeks, suggesting downstream effects rather than simple neurotransmitter deficiency. The neuroplasticity theory addresses these limitations by focusing on brain-derived neurotrophic factor (BDNF) and synaptic plasticity. BDNF levels are reduced in depression and increase with successful treatment. The hippocampus shows volume reduction in chronic depression, possibly reflecting impaired neurogenesis. Chronic stress and elevated glucocorticoids impair neuroplasticity. Antidepressants, regardless of their immediate mechanism, ultimately promote BDNF expression and neuroplasticity, explaining the delayed therapeutic onset. Neural circuit abnormalities are consistently identified in depression. The prefrontal cortex, responsible for executive function and emotion regulation, shows hypoactivity, contributing to cognitive symptoms and impaired top-down emotional control. The limbic system, particularly the amygdala, shows hyperactivity, contributing to negative emotional bias. The hypothalamic-pituitary-adrenal (HPA) axis is frequently hyperactive, with elevated cortisol and impaired feedback inhibition. The default mode network shows increased activity, correlating with rumination and self-referential negative thinking. Genetic factors contribute approximately 40% of depression risk, though no single gene accounts for substantial risk. Gene-environment interactions, such as the interaction between serotonin transporter polymorphisms (5-HTTLPR) and early life stress, influence vulnerability. Current understanding emphasizes polygenic risk involving multiple genes with small individual effects. Panel A diagrams the monoamine neurotransmitter systems implicated in depression (serotonin, norepinephrine, dopamine) showing their projections and functional roles. Panel B illustrates the neuroplasticity hypothesis showing stress effects on BDNF and hippocampal neurogenesis, and how antidepressants reverse these changes. Panel C depicts the HPA axis dysregulation in depression with elevated cortisol and impaired negative feedback. Panel D shows neural circuits involved including prefrontal cortex, amygdala, and default mode network. --- ### III. Antidepressant Medications Antidepressant medications remain the cornerstone of moderate-to-severe depression treatment. Understanding their mechanisms, clinical applications, and side effects enables rational prescribing. Selective serotonin reuptake inhibitors (SSRIs) are first-line agents due to their efficacy, tolerability, and safety in overdose. They selectively inhibit the serotonin transporter, increasing synaptic serotonin. Fluoxetine has the longest half-life, is activating, and is often well-tolerated but may cause more drug interactions due to CYP2D6 inhibition. Sertraline has minimal drug interactions and is often preferred when interactions are a concern. Paroxetine has a shorter half-life leading to more discontinuation symptoms, has anticholinergic effects, and should be avoided in pregnancy due to cardiac malformation risk. Citalopram is well-tolerated but carries dose-dependent QT prolongation risk. Escitalopram, the S-enantiomer of citalopram, may have fewer side effects. Common SSRI side effects include gastrointestinal disturbance (nausea, diarrhea), sexual dysfunction (decreased libido, anorgasmia), initial anxiety activation, weight gain with long-term use, and the risk of serotonin syndrome with drug combinations. Serotonin-norepinephrine reuptake inhibitors (SNRIs) inhibit both serotonin and norepinephrine transporters, providing dual mechanism action. Venlafaxine may be more effective than SSRIs in some patients but can increase blood pressure at higher doses. Duloxetine is also FDA-approved for chronic pain, diabetic neuropathy, and fibromyalgia, making it useful when depression and pain co-occur. Side effects are similar to SSRIs with additional risk of hypertension. Other antidepressants offer alternative mechanisms. Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI) with no sexual side effects and weight-neutral to weight-loss profile; it is also used for smoking cessation but carries seizure risk at higher doses. Mirtazapine blocks alpha-2 adrenergic autoreceptors and serotonin 5-HT2 and 5-HT3 receptors; it is sedating and causes weight gain but is useful for depression with insomnia and poor appetite. Trazodone is primarily a 5-HT2A antagonist with weak serotonin reuptake inhibition; it is used mainly for insomnia as an adjunct and carries rare priapism risk. Newer agents include vilazodone and vortioxetine with multimodal mechanisms. Older antidepressants remain useful in specific situations. Tricyclic antidepressants (TCAs) such as amitriptyline and nortriptyline are effective but carry significant anticholinergic effects, cardiac toxicity, and lethality in overdose. Monoamine oxidase inhibitors (MAOIs) such as phenelzine and tranylcypromine are highly effective but require dietary restrictions to avoid tyramine-induced hypertensive crisis and have numerous drug interactions. Panel A illustrates SSRI mechanism at the synapse showing serotonin transporter blockade and increased synaptic serotonin. Panel B compares antidepressant classes by mechanism of action with a receptor/transporter binding profile chart. Panel C presents a treatment algorithm showing first-line (SSRI) through alternatives based on response and tolerability. Panel D tabulates key side effects by drug class with clinical management strategies. --- ### IV. Treatment Approach to Depression Effective depression treatment requires a systematic approach addressing medication selection, treatment phases, and management of non-response. Treatment selection integrates multiple factors. Severity guides modality choice: mild depression may respond to psychotherapy alone, while moderate-to-severe depression typically requires medication. Prior treatment response strongly predicts future response—use previously effective medications. Side effect profiles should be matched to patient concerns: avoid SSRIs if sexual function is prioritized; consider mirtazapine for patients with insomnia and poor appetite; use bupropion if weight is a concern. Comorbid conditions influence selection: duloxetine for coexisting pain, bupropion for smoking cessation. Cost and access, including generic availability, affect real-world adherence. Treatment follows three phases. The acute phase (6-12 weeks) aims to achieve remission (resolution of all symptoms), not just response (50% improvement). Full therapeutic doses and adequate duration are essential—most antidepressants require 4-6 weeks for effect assessment. The continuation phase (4-9 months) prevents relapse by maintaining the same medication and dose that achieved remission. Premature discontinuation dramatically increases relapse risk. The maintenance phase (years to lifelong) prevents recurrence in patients with multiple episodes, chronic depression, or severe episodes. Longer maintenance is indicated with each subsequent episode. Treatment-resistant depression (TRD) is defined as failure of at least two adequate antidepressant trials (appropriate dose and duration). Options include augmentation strategies (adding a second agent to the current antidepressant), switching strategies (changing to a different class), and combination strategies (combining two antidepressants). Augmentation options include lithium (well-established), atypical antipsychotics (aripiprazole, quetiapine, olanzapine—all FDA-approved for augmentation), and thyroid hormone (T3). Somatic treatments for severe or refractory depression include electroconvulsive therapy (ECT)—the most effective treatment for severe depression, transcranial magnetic stimulation (TMS)—effective and well-tolerated, and ketamine/esketamine—rapid-acting, particularly for suicidal ideation. Electroconvulsive therapy deserves specific attention. Indications include severe depression, treatment resistance, catatonia, depression in pregnancy (when medications are problematic), and need for rapid response. It is the most effective treatment for major depression, with response rates exceeding 70%. Side effects are primarily cognitive—transient memory impairment that usually resolves. The mechanism involves inducing a controlled generalized seizure under anesthesia. Panel A presents a treatment selection algorithm incorporating severity, prior response, side effect profile, and comorbidities. Panel B illustrates the three treatment phases (acute, continuation, maintenance) with timelines and goals. Panel C displays TRD management strategies including augmentation options with their evidence base. Panel D shows ECT indication criteria and procedure overview with expected outcomes. --- ### V. Bipolar Disorder Overview Bipolar disorder encompasses a spectrum of conditions characterized by episodes of mania or hypomania alternating with depressive episodes. Recognition and appropriate treatment differ substantially from unipolar depression. The bipolar spectrum includes several diagnoses. Bipolar I disorder requires at least one manic episode—this is the defining criterion. Depressive episodes are common but not required for diagnosis. Bipolar II disorder requires at least one hypomanic episode AND at least one major depressive episode; mania has never occurred. Cyclothymic disorder involves chronic fluctuating mood disturbance with hypomanic and depressive symptoms that do not meet full episode criteria, lasting at least two years. Other specified bipolar disorder captures presentations not meeting full criteria. Epidemiology reveals distinct patterns. The bipolar spectrum affects approximately 2.5% of the population. Unlike unipolar depression, sex distribution is equal. Age of onset is typically late adolescence to mid-20s, earlier than unipolar depression. Heritability is approximately 80%—the highest of any psychiatric disorder—indicating strong genetic contribution. First-degree relatives of bipolar patients have approximately 10% risk of bipolar disorder. Distinguishing bipolar I from bipolar II is clinically important. In bipolar I, mania is required and may occur without depressive episodes; psychotic features can occur during mania; and hospitalization is often required during manic episodes. In bipolar II, hypomania is required but mania never occurs; depressive episodes are required and often predominate the clinical picture; and impairment is primarily from depression rather than elevated mood states. Bipolar II is not a "milder" form—depression is often severe and chronic, and suicide risk is substantial. Distinguishing bipolar from unipolar depression is critical because treatment differs dramatically. Features suggesting bipolar include: family history of bipolar disorder, earlier age of onset (before age 25), more numerous depressive episodes, atypical features (hypersomnia, hyperphagia), psychotic features at a young age, poor response to antidepressants, rapid cycling with antidepressant treatment, and antidepressant-induced mood switching. Panel A compares the bipolar spectrum disorders (bipolar I, II, cyclothymic) showing episode types and diagnostic requirements. Panel B illustrates the mood episode timeline for bipolar I versus bipolar II showing the presence or absence of mania. Panel C presents features distinguishing bipolar from unipolar depression in a comparison format. Panel D displays heritability and genetic risk data with implications for family screening. --- ### VI. Manic Episode The manic episode is the hallmark of bipolar I disorder. Recognition of manic symptoms is essential for accurate diagnosis. DSM-5 criteria require a distinct period of abnormally and persistently elevated, expansive, or irritable mood AND increased goal-directed activity or energy, lasting at least one week (or any duration if hospitalization is required). During this period, three or more symptoms must be present (four if mood is only irritable) and represent a noticeable change from baseline. The DIG FAST mnemonic captures manic symptoms: Distractibility (attention easily drawn to unimportant stimuli), Insomnia (decreased need for sleep—feeling rested after only a few hours, distinct from insomnia with fatigue), Grandiosity (inflated self-esteem, may reach delusional proportions), Flight of ideas (racing thoughts, subjective experience of thoughts moving faster than speech), Activity increase (increased goal-directed activity socially, at work, or sexually; or psychomotor agitation), Speech (pressured, rapid, difficult to interrupt), Taking risks (excessive involvement in pleasurable activities with high potential for painful consequences—spending sprees, sexual indiscretions, foolish investments). Severity ranges from mild (meeting minimum criteria with mild impairment) through moderate (increased activity with impaired judgment) to severe (marked impairment, may require supervision or hospitalization). Psychotic features—delusions or hallucinations—may occur in severe mania and are often mood-congruent (grandiose or persecutory themes consistent with elevated mood). The hypomanic episode shares the same symptom criteria but differs in several critical ways: duration is at least four consecutive days (not one week); there is no marked impairment in functioning—the episode is an unequivocal change observable by others but does not cause severe dysfunction; psychotic features are absent (their presence would upgrade to mania); and hospitalization is not required. The distinction matters because hypomania defines bipolar II, while mania defines bipolar I. Panel A illustrates the DIG FAST mnemonic with each symptom defined and clinical examples provided. Panel B compares mania versus hypomania with criteria differences highlighted including duration, impairment level, and psychotic features. Panel C displays mania severity levels with corresponding clinical features and management implications. Panel D presents examples of mood-congruent psychotic features in mania including grandiose and persecutory delusions. --- ### VII. Bipolar Depression Depressive episodes predominate the clinical course of bipolar disorder, accounting for three times more time than mood elevation in bipolar I and even greater proportions in bipolar II. Management of bipolar depression differs substantially from unipolar depression. Clinical features of bipolar depression largely overlap with major depressive disorder—the same SIG E CAPS criteria apply. However, certain features are more common in bipolar depression: atypical features (hypersomnia, hyperphagia, leaden paralysis, rejection sensitivity), psychomotor retardation more than agitation, and longer episode duration. Distinguishing bipolar from unipolar depression retrospectively relies on history of mania or hypomania, family history, and the clinical features suggesting bipolarity discussed previously. Treatment of bipolar depression differs critically from unipolar depression. The central concern with antidepressant use is the risk of mood switching—antidepressants can trigger manic or hypomanic episodes. Additionally, antidepressants may induce rapid cycling (four or more episodes per year). Current guidelines recommend using mood stabilizers and atypical antipsychotics as first-line treatments for bipolar depression, with antidepressants reserved for adjunctive use (always with a mood stabilizer) or avoided entirely in some cases. First-line treatments for bipolar depression include quetiapine (FDA-approved, effective as monotherapy), lurasidone (FDA-approved, effective with food for absorption), olanzapine-fluoxetine combination (FDA-approved), and lamotrigine (effective for maintenance and mild-to-moderate acute depression). If antidepressants are used, they should always be combined with a mood stabilizer, and bupropion or SSRIs are preferred over TCAs or SNRIs, which have higher switching risk. Antidepressants should be discontinued after remission is achieved. Panel A compares features more common in bipolar versus unipolar depression in a side-by-side format. Panel B illustrates the risk of antidepressant-induced mood switching with a mood timeline showing depression converting to mania. Panel C presents first-line treatment options for bipolar depression with their FDA approval status and evidence base. Panel D shows a bipolar depression treatment algorithm with medication sequencing. --- ### VIII. Mood Stabilizers Mood stabilizers are the foundation of bipolar disorder treatment, preventing both manic and depressive episodes. The term encompasses several medication classes. Lithium remains the prototypical mood stabilizer with over 60 years of clinical use. Its mechanism involves multiple targets including GSK-3 inhibition and effects on intracellular signaling; the precise mechanism is incompletely understood. Indications include acute mania, maintenance treatment, and—uniquely—demonstrated anti-suicide effect, making it particularly valuable for patients with suicidality. Monitoring requirements include serum levels (therapeutic range 0.6-1.2 mEq/L for maintenance, higher for acute mania), renal function (lithium is renally excreted and can cause nephrogenic diabetes insipidus and chronic nephropathy), thyroid function (causes hypothyroidism in up to 20%), and calcium (associated with hyperparathyroidism). Side effects include tremor, polyuria/polydipsia, cognitive dulling, weight gain, and GI disturbance. Toxicity occurs at levels above 1.5 mEq/L with confusion, ataxia, coarse tremor; severe toxicity causes seizures, cardiac arrhythmias, and coma. Lithium has a narrow therapeutic index, and toxicity is precipitated by dehydration, NSAIDs, ACE inhibitors, and thiazides. Valproate (valproic acid, divalproex) is a first-line option for acute mania, mixed states, and rapid cycling. Its mechanism involves GABA enhancement and sodium channel effects. Monitoring includes liver function tests, complete blood count, and drug levels. Side effects include weight gain, hair loss, tremor, GI disturbance, and potentially fatal hepatotoxicity (rare, mainly in children). Critically, valproate is highly teratogenic, causing neural tube defects in 1-2% and neurodevelopmental effects, and should be avoided in women of childbearing potential. Lamotrigine is distinct from other mood stabilizers: it is effective for bipolar depression and maintenance (especially depression prevention) but NOT effective for acute mania. Mechanism involves sodium channel blockade and glutamate inhibition. The critical side effect is Stevens-Johnson syndrome (SJS), a potentially fatal skin reaction requiring slow titration over 6-8 weeks to minimize risk. Interaction with valproate doubles lamotrigine levels, requiring even slower titration. Carbamazepine is effective for mania and mixed states. Side effects include hyponatremia, aplastic anemia, SJS (HLA-B*1502 testing recommended in Asian patients), and significant drug interactions due to CYP induction. Panel A presents lithium's mechanism of action, monitoring requirements, and therapeutic range with toxicity levels indicated. Panel B compares mood stabilizers across efficacy domains (mania, depression, maintenance) and key monitoring requirements. Panel C illustrates the lamotrigine titration schedule with SJS warning signs. Panel D shows drug-drug interactions affecting lithium levels with management strategies. --- ### IX. Atypical Antipsychotics in Bipolar Disorder Second-generation (atypical) antipsychotics have become central to bipolar disorder management, with FDA approvals across mania, depression, and maintenance indications. Quetiapine has the broadest evidence base with FDA approval for acute mania, bipolar depression, and maintenance. For depression, it is effective as monotherapy at doses of 300-600 mg. Side effects include sedation, weight gain, metabolic effects, and orthostatic hypotension. Olanzapine is highly effective for acute mania but has significant metabolic liability—weight gain and diabetes risk are highest among atypicals. The olanzapine-fluoxetine combination (OFC) is FDA-approved for bipolar depression. Olanzapine is also approved for maintenance. Aripiprazole has a unique mechanism as a partial dopamine agonist, providing D2 modulation rather than pure antagonism. It is FDA-approved for acute mania and maintenance but not depression. Akathisia is the most common limiting side effect. The metabolic profile is more favorable than olanzapine or quetiapine. Risperidone is effective for acute mania and maintenance. It carries higher risk of extrapyramidal symptoms (EPS) at higher doses and causes hyperprolactinemia, which can lead to gynecomastia, galactorrhea, and sexual dysfunction. Lurasidone is FDA-approved for bipolar depression (not mania) and has a favorable metabolic profile. It must be taken with food (at least 350 calories) for adequate absorption. Cariprazine, a newer agent, is FDA-approved for both acute mania and bipolar depression. Side effect considerations guide selection. Metabolic effects (weight gain, dyslipidemia, diabetes) are highest with olanzapine and quetiapine, requiring metabolic monitoring with all atypicals. EPS risk is highest with risperidone. Sedation is prominent with quetiapine and olanzapine. QT prolongation is a concern with ziprasidone. Acute mania treatment typically requires combination therapy for moderate-to-severe episodes. Options include mood stabilizer alone, atypical antipsychotic alone, or combination (often most effective). Benzodiazepines (lorazepam, clonazepam) are useful adjuncts for agitation and insomnia. Panel A tabulates FDA-approved atypical antipsychotics for bipolar disorder showing approvals across mania, depression, and maintenance indications. Panel B ranks agents by metabolic risk, EPS risk, and sedation for side effect comparison. Panel C presents an acute mania treatment algorithm progressing from monotherapy to combination therapy. Panel D illustrates metabolic monitoring requirements including baseline and ongoing assessments. --- ### X. Psychotherapy and Special Populations Psychotherapy complements pharmacotherapy in mood disorders, with specific approaches having strong evidence bases. Special populations require modified treatment approaches. Psychotherapy for depression includes several evidence-based modalities. Cognitive behavioral therapy (CBT) identifies and challenges negative automatic thoughts, modifies cognitive distortions, and incorporates behavioral activation to increase engagement with rewarding activities. Interpersonal therapy (IPT) focuses on interpersonal relationships, role transitions, grief, and interpersonal deficits as contributors to and consequences of depression. Behavioral activation specifically targets decreased activity and withdrawal, systematically scheduling pleasurable and mastery activities. Mindfulness-based cognitive therapy (MBCT) combines mindfulness practices with CBT elements and is particularly effective for relapse prevention in recurrent depression. Psychotherapy for bipolar disorder emphasizes psychoeducation—understanding the illness, recognizing early warning signs of episodes, and importance of medication adherence. CBT adapted for bipolar disorder addresses mood monitoring, cognitive restructuring, and management of residual symptoms. Interpersonal and social rhythm therapy (IPSRT) focuses on stabilizing daily routines and sleep-wake cycles, which influence mood stability. Family-focused therapy involves family members in understanding the illness, improving communication, and reducing expressed emotion, which predicts relapse. Special populations require careful management. Pregnancy presents challenges in mood disorder treatment. For depression, lamotrigine and certain SSRIs (sertraline, citalopram) have relatively reassuring data; paroxetine and valproate should be avoided. For bipolar disorder, lithium carries cardiac teratogenicity risk (Ebstein's anomaly) requiring fetal echocardiography; valproate is contraindicated; lamotrigine is relatively safer. ECT is safe and effective in pregnancy when medication options are limited. The elderly require lower starting doses, consideration of drug interactions, and avoidance of medications with anticholinergic effects. Children and adolescents have limited approved options; fluoxetine is FDA-approved for pediatric depression, and the black box warning about suicidality requires monitoring. Medically ill patients commonly develop depression, particularly post-MI and post-stroke, where depression worsens outcomes and warrants treatment. Suicide risk in mood disorders demands attention. Up to 15% of individuals with severe depression die by suicide. Bipolar disorder carries elevated risk, particularly during mixed states and depressive episodes. Lithium uniquely reduces suicide risk independent of its mood-stabilizing effects. The FDA black box warning on antidepressants notes increased suicidality in youth, requiring close monitoring; however, untreated depression also carries high suicide risk. Panel A illustrates the CBT cognitive triangle showing the relationship between thoughts, feelings, and behaviors with examples of therapeutic interventions. Panel B compares psychotherapy modalities for depression (CBT, IPT, behavioral activation, MBCT) with their key components and evidence base. Panel C presents medication considerations in pregnancy organized by trimester and disorder. Panel D shows suicide risk factors in mood disorders with protective factors and intervention strategies. --- ## Summary - MDD diagnosis requires five of nine SIG E CAPS symptoms for at least two weeks, including depressed mood or anhedonia; specifiers (melancholic, atypical, psychotic, peripartum, seasonal) guide treatment - Depression neurobiology involves monoamine deficiency, impaired neuroplasticity with reduced BDNF, HPA axis hyperactivity, and neural circuit abnormalities in prefrontal cortex and limbic system - SSRIs are first-line antidepressants; SNRIs offer dual mechanism; bupropion avoids sexual and weight side effects; mirtazapine helps insomnia and appetite - Treatment phases: acute (achieve remission, 6-12 weeks), continuation (prevent relapse, 4-9 months), maintenance (prevent recurrence, years); TRD options include augmentation, switching, ECT, ketamine - Bipolar I requires at least one manic episode; bipolar II requires hypomania plus major depression; mania (DIG FAST) lasts at least one week with marked impairment; hypomania lasts at least four days without marked impairment - Bipolar depression treatment differs from unipolar: quetiapine, lurasidone, lamotrigine are first-line; antidepressants carry mood-switching risk and should be used cautiously with mood stabilizer - Lithium is the prototypical mood stabilizer with anti-suicide effect; requires level, renal, and thyroid monitoring; narrow therapeutic index with toxicity above 1.5 mEq/L - Valproate effective for mania but highly teratogenic; lamotrigine effective for depression maintenance but requires slow titration due to SJS risk --- ## Key Terms | Term | Definition | |------|------------| | Anhedonia | Inability to experience pleasure from activities previously found enjoyable | | Major depressive episode | Period of at least two weeks with five or more depressive symptoms causing significant impairment | | Mania | Distinct period of elevated or irritable mood with increased energy lasting at least one week with marked impairment | | Hypomania | Period of elevated mood and energy lasting at least four days without marked impairment or psychotic features | | Mood stabilizer | Medication preventing manic and depressive episodes, including lithium and certain anticonvulsants | | Treatment-resistant depression | Failure of at least two adequate antidepressant trials | | Mixed features | Presence of opposite-pole symptoms during a mood episode (depressive symptoms during mania or vice versa) | | Rapid cycling | Four or more mood episodes within a 12-month period | | Melancholic features | Severe depression subtype with profound anhedonia, morning worsening, and psychomotor changes | | Atypical features | Depression subtype with mood reactivity, hypersomnia, hyperphagia, and leaden paralysis | --- *This content is subject to the [MIT License](https://opensource.org/licenses/MIT). © 2024–2026 Hibbert School of Medicine.*