14.1 Depressive Disorders, Bipolar Affective Disorder & Suicide Risk Assessment

Diagnostic Classification & Clinical Evaluation of Major Depressive Disorder

Major Depressive Disorder (MDD) represents a leading cause of functional disability worldwide and across the Caribbean healthcare landscape. Accurate recognition demands a rigorous clinical interview that differentiates unipolar depression from normal bereavement, adjustment disorders, bipolar affective illness, and organic medical conditions mimicking mood disorders.

DSM-5 Diagnostic Criteria & The SIGECAPS Framework

According to the DSM-5, a diagnosis of Major Depressive Disorder requires the presence of at least 5 of the following 9 symptoms during the same 2-week period, representing a clear departure from previous functioning. At least one of the symptoms must be either depressed mood or loss of interest or pleasure (anhedonia):

• S – Sleep Disturbances: Insomnia (characteristically terminal insomnia with early morning awakening 2 to 3 hours prior to the alarm) or hypersomnia.
• I – Interest Deficit (Anhedonia): Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day.
• G – Guilt & Worthlessness: Excessive, inappropriate, or delusional feelings of worthlessness or guilt (not merely self-reproach about being sick).
• E – Energy Deficit: Pervasive fatigue, loss of stamina, or severe anergia nearly every day.
• C – Concentration Impairment: Diminished ability to think, concentrate, or make minor decisions, often reported by family members as cognitive slowing (pseudodementia in the elderly).
• A – Appetite & Weight Alterations: Significant weight loss when not dieting or weight gain (a change of more than 5% of body weight in a month), or decrease/increase in appetite nearly every day.
• P – Psychomotor Alterations: Psychomotor agitation (pacing, hand-wringing, inability to sit still) or retardation (slowed speech, increased response latency, poverty of movement) observable by others.
• S – Suicidal Ideation: Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or specific plan for committing suicide.

Diagnostic Requirements: Symptoms must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning, and must not be attributable to the direct physiological effects of a substance or general medical condition, nor better explained by a schizoaffective spectrum disorder.

Systematic Exclusion of Organic & Medical Mimics

Before initiating psychotropic therapy, the clinician must systematically exclude reversible biological etiologies through targeted diagnostic testing:

1. Endocrine Pathologies: Primary hypothyroidism is the most frequent medical mimic; obtain serum Thyroid-Stimulating Hormone (TSH) and Free T4. Additional endocrine triggers include Cushing's syndrome (hypercortisolemia), Addison's disease (adrenal insufficiency), and primary hyperparathyroidism (hypercalcemia presenting with fatigue, constipation, and depression).
2. Hematologic & Nutritional Deficiencies: Severe iron deficiency anemia and vitamin B12 (cobalamin) or folate deficiency induce profound fatigue, cognitive blunting, and depressive affect. Use a full blood count, ferritin, B12/folate levels and blood film when the history, examination or initial results suggest anaemia or nutritional deficiency.
3. Cerebrovascular & Neurological Disorders: Post-stroke depression occurs in up to 30% to 50% of patients following ischemic or hemorrhagic stroke, especially with left frontal cortical and basal ganglia lesions. Early-stage Parkinson's disease, multiple sclerosis, and normal pressure hydrocephalus also frequently present with prominent mood changes.
4. Chronic Infectious Diseases: HIV-associated neurocognitive and depressive disorders, chronic hepatitis C, and neurosyphilis (obtain VDRL/RPR) should be actively investigated in regional clinical practice.
5. Medication-Induced Depressive Disorders: Systemic corticosteroids (prednisone, dexamethasone), interferon-alpha, centrally acting antihypertensives (methyldopa, reserpine, propranolol), oral contraceptive agents, and withdrawal from psychostimulants (cocaine, amphetamines) or chronic alcohol misuse.

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Pharmacotherapy of Depressive Disorders

Modern antidepressant selection is governed by side effect tolerability, safety in overdose, comorbid medical conditions, and previous individual or familial drug responses.

1. Selective Serotonin Reuptake Inhibitors (SSRIs)

• First-Line Agents: Sertraline, escitalopram, citalopram, and fluoxetine.
• Mechanism of Action: Selectively block the presynaptic serotonin reuptake transporter (SERT / SLC6A4), increasing synaptic serotonin (5-HT) availability and subsequently downregulating inhibitory 5-HT1A somatodendritic autoreceptors over time.
• Clinical Pharmacokinetics & Onset: Antidepressant efficacy exhibits a characteristic therapeutic lag of 2 to 4 weeks (and up to 6 to 8 weeks for full clinical response). Patients must be educated that physical vegetative symptoms (sleep, energy, appetite) generally improve before mood and suicidal ideation lift.
• Adverse Effects: Early transient gastrointestinal upset (nausea, diarrhea due to 5-HT3 stimulation), tension headache, and paradoxical agitation/anxiety; long-term sexual dysfunction (delayed ejaculation, anorgasmia, decreased libido in 30% to 50% of patients); hyponatremia secondary to Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), particularly in elderly patients on diuretics.
• Discontinuation Syndrome: Abrupt cessation of SSRIs with short half-lives (e.g., paroxetine, sertraline) triggers dizziness, electric shock-like sensations (brain zaps), paresthesias, insomnia, and flu-like symptoms. Fluoxetine has an active metabolite (norfluoxetine) with an elimination half-life of 7 to 15 days, self-tapering and conferring the lowest risk of withdrawal.

2. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

• Agents: Venlafaxine, duloxetine, desvenlafaxine.
• Mechanism: Dual inhibition of SERT and the norepinephrine transporter (NET). Duloxetine exhibits balanced SERT and NET inhibition across therapeutic doses; venlafaxine blocks SERT at low doses (< 150 mg/day) and NET at higher doses (>= 150-225 mg/day).
• Clinical Utility: First-line alternative for major depression, especially when complicated by comorbid chronic neuropathic pain, diabetic peripheral neuropathy, or fibromyalgia.
• Key Adverse Effects: Noradrenergic stimulation can cause dose-dependent sustained hypertension (mandatory blood pressure monitoring), tachycardia, diaphoresis, and dry mouth.

3. Tricyclic Antidepressants (TCAs)

• Agents: Amitriptyline, imipramine, nortriptyline, clomipramine.
• Mechanism: Block SERT and NET, but also act as potent competitive antagonists at muscarinic acetylcholine (M1), histamine (H1), and alpha-1 adrenergic receptors.
• Adverse Profile: Anticholinergic toxicity (dry mouth, blurred vision, urinary retention, severe constipation, precipitation of acute angle-closure glaucoma, delirium in the elderly); antihistaminic sedation and weight gain; alpha-1 blockade causing orthostatic hypotension and reflex tachycardia.
• Lethality in Overdose: TCAs possess a notoriously narrow therapeutic index. Ingestion of as little as 10 to 20 mg/kg can be fatal. TCAs block myocardial fast inward voltage-gated sodium channels (phase 0 depolarization), prolonging the QRS duration (> 100 ms predicts seizures; > 160 ms predicts life-threatening ventricular arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointes).
• TCA Overdose Management: Secure airway and establish continuous ECG monitoring. The specific antidote is Intravenous Sodium Bicarbonate (1 to 2 mmol/kg IV bolus, repeated to maintain blood arterial pH between 7.45 and 7.55 and narrow the QRS complex below 100 ms). Alkalinization decreases the fraction of free active ionized drug, and the high extracellular sodium load overcomes competitive sodium channel blockade.

4. Monoamine Oxidase Inhibitors (MAOIs)

• Agents: Phenelzine, tranylcypromine, isocarboxazid, moclobemide (reversible MAO-A inhibitor).
• Mechanism: Phenelzine, tranylcypromine and isocarboxazid irreversibly inhibit MAO-A and MAO-B; moclobemide reversibly inhibits MAO-A. These actions reduce monoamine breakdown.
• The Tyramine "Cheese Reaction": Ingestion of foods rich in tyramine (aged cheeses, cured meats, red wine, draft beer, fava beans, marmite, soy sauce) precipitates a life-threatening hypertensive crisis. Dietary tyramine is normally metabolized by gastrointestinal and hepatic MAO-A; with MAOI inhibition, unmetabolized tyramine enters the systemic circulation, is taken up into presynaptic adrenergic terminals via NET, and displaces massive quantities of vesicular norepinephrine into the synaptic cleft.
• Washout Period: Switch under specialist guidance: allow at least 14 days after an irreversible MAOI before most other antidepressants, but moclobemide usually requires 24 hours before an SSRI/SNRI. The interval before starting an MAOI depends on the stopped drug; after fluoxetine, wait 5–6 weeks to prevent serotonin toxicity.

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Bipolar Affective Disorders: Diagnostic Divergence & Mood Stabilizers

Bipolar affective disorder is a chronic, relapsing condition characterized by pathological oscillations in mood, energy, and activity levels. Accurate differentiation between unipolar depression and bipolar depression is critical because antidepressant monotherapy in bipolar patients risks triggering manic induction, rapid cycling, and clinical instability.

Diagnostic Divergence: Bipolar I vs. Bipolar II vs. Cyclothymia

• Bipolar I Disorder: Defined by the occurrence of at least one lifetime manic episode. Major depressive episodes and hypomanic episodes are common throughout the disease course but are not strictly required for DSM-5 diagnosis. A manic episode requires an abnormally and persistently elevated, expansive, or irritable mood and abnormally increased goal-directed activity or energy, lasting at least 1 week (or any duration if hospitalization is necessary), present most of the day, nearly every day.
• Diagnostic Mnemonic for Mania – DIG FAST:
  • D – Distractibility: Attention too easily drawn to unimportant or irrelevant external stimuli.
  • I – Indiscretion / Impulsivity: Excessive involvement in activities with high potential for painful consequences (unrestrained buying sprees, sexual indiscretions, foolish business investments).
  • G – Grandiosity: Inflated self-esteem or grandiose beliefs (special powers, divine missions, unchallengeable authority).
  • F – Flight of Ideas: Subjective experience that thoughts are racing, accompanied by rapid shifts in topics.
  • A – Activity Increase: Marked increase in goal-directed activity (socially, at work, or sexually) or psychomotor agitation.
  • S – Sleep Deficit: Decreased need for sleep (e.g., feels rested after only 2 or 3 hours of sleep; distinct from insomnia where the patient desires sleep but cannot achieve it).
  • T – Talkativeness (Pressured Speech): Speech is rapid, loud, continuous, and difficult to interrupt.
• Bipolar II Disorder: Characterized by a lifetime clinical course of at least one hypomanic episode AND at least one major depressive episode. A hypomanic episode lasts at least 4 consecutive days with DIG FAST symptoms, represents an unequivocal change in functioning, but is NOT severe enough to cause marked impairment in social or occupational functioning, does NOT require hospitalization, and NEVER features psychotic symptoms. If psychosis or hospitalization occurs, the episode is categorized as mania, establishing a diagnosis of Bipolar I.
• Cyclothymic Disorder: For at least 2 years (1 year in children/adolescents), numerous periods with hypomanic symptoms that do not meet full hypomania criteria and depressive symptoms that do not meet full major depressive episode criteria.

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Comparative Pharmacodynamics of Mood Stabilizers

Clinical Management of Lithium Toxicity

Lithium has an exceptionally narrow therapeutic window. Serum levels must be drawn precisely 12 hours after the evening dose.

• Precipitating Factors: Volume depletion, dehydration (tropical heat, gastroenteritis), sodium restriction, and concurrent administration of drugs that reduce renal lithium clearance: Thiazide Diuretics (induce proximal tubule sodium and lithium reabsorption), NSAIDs (inhibit renal prostaglandin synthesis, lowering GFR), and ACE Inhibitors / ARBs.
• Clinical Manifestations:
  • Mild Toxicity (1.5 to 2.0 mmol/L): Coarse tremor, persistent nausea, vomiting, watery diarrhea, lethargy, muscle weakness.
  • Moderate to Severe Toxicity (> 2.0 to 2.5 mmol/L): Severe ataxia, dysarthria, nystagmus, myoclonic twitches, hyperreflexia, visual hallucinations, acute kidney injury, seizures, stupor, and coma.
• Emergency Management: Discontinue lithium immediately. Administer aggressive intravenous hydration with 0.9% Normal Saline to restore intravascular volume and promote renal lithium clearance. Hemodialysis is recommended for reduced consciousness, seizures or life-threatening dysrhythmias regardless of lithium level, or impaired kidney function with lithium >4.0 mmol/L. EXTRIP also suggests it for lithium >5.0 mmol/L, significant confusion, or an expected time >36 hours to reach <1.0 mmol/L with optimal care. Seek urgent toxicology/nephrology advice and monitor serial levels for rebound.
• Teratogenic Profile: Lithium exposure during the first trimester of pregnancy carries an increased risk of Ebstein's Anomaly (downward apical displacement of the tricuspid valve leaflets into the right ventricle, resulting in tricuspid regurgitation and severe atrialization of the right ventricle).

Teratogenicity of Anticonvulsant Mood Stabilizers

• Valproate: Carries the highest teratogenic risk of all psychotropic medications, causing a 1% to 2% incidence of neural tube defects (spina bifida aperta, anencephaly), facial clefts, and significant long-term neurodevelopmental delays (IQ deficits of 8-11 points). Valproate is strictly contraindicated in women of childbearing potential unless fully refractory to all other options and enrolled in a pregnancy prevention program with high-dose folate supplementation (5 mg daily).

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Suicide Risk Assessment & Clinical Triage in Caribbean Practice

Suicide represents a profound, preventable tragedy. In several Caribbean territories—notably Guyana, Trinidad and Tobago, and rural agricultural belts in Jamaica—suicide rates are compounded by easy domestic access to lethal agricultural chemicals, particularly organophosphate insecticides and the bipyridyl herbicide paraquat (Gramoxone). Registered medical practitioners must be adept in rapid risk stratification, lethal means restriction, and involuntary protective containment.

The Clinical Interview: Inquiring Directly

• Evidence-Based Rule: Asking directly, clearly, and empathetically about suicidal thoughts does not plant ideas or increase the risk of suicide. On the contrary, it provides immediate psychological relief, validates emotional distress, and opens the door for lifesaving intervention.
• Graded Exploration: Inquire systematically: (1) Passive thoughts of death ("Do you ever wish you would not wake up in the morning?"), (2) Active suicidal ideation ("Have you had thoughts of ending your life?"), (3) Plan ("Have you thought about how you might do it?"), (4) Intent ("Do you intend to act on these thoughts?"), and (5) Lethal Means Access ("Do you have access to medications, firearms, or agricultural chemicals at home?").

Static vs. Dynamic Suicide Risk Factors

• Static (Unchangeable) Risk Factors: Male sex (higher completion rate, whereas females have higher attempt rates); age extremes (< 19 or > 45 years); prior suicide attempt (the single strongest clinical predictor of completed suicide); family history of suicide; chronic physical illness or severe intractable pain.
• Dynamic (Modifiable) Clinical Factors: Active substance or alcohol intoxication; acute psychotic symptoms (command auditory hallucinations directing self-harm); severe psychic agitation or akathisia; global hopelessness; active domestic conflict or bereavement; immediate access to lethal means.
• The SAD PERSONS Mnemonic: A historical checklist of risk factors; it must not determine admission or discharge:
  • S – Sex (Male = 1)
  • A – Age (< 19 or > 45 years = 1)
  • D – Depression or severe mood disorder (= 1)
  • P – Previous suicide attempt (= 1)
  • E – Ethanol or drug abuse (= 1)
  • R – Rational thinking loss (psychosis, severe depression = 1)
  • S – Social support lacking (= 1)
  • O – Organized plan with lethal intent (= 1)
  • N – No spouse (divorced, separated, widowed, single = 1)
  • S – Sickness (chronic, debilitating medical illness = 1)
  • Clinical Use: Do not use the score or a low/medium/high label to predict suicide or decide discharge. Formulate the person's immediate safety needs from current intent, plans, means, mental state, supports and ability to engage in care; arrange urgent specialist assessment when safety is uncertain.

Involuntary Admission & Regional Mental Health Legislation

Emergency psychiatric care follows the law of the jurisdiction, rather than a single regional detention rule. Maintain immediate observation and means restriction, seek urgent psychiatric assessment and offer voluntary care whenever feasible.

1. Compulsory Assessment/Admission: If voluntary care is refused and immediate safety cannot be maintained, assess the national statutory criteria, authorised applicant/certifier and least restrictive safe option. Document the grounds and the person's rights; mental illness alone does not remove decision-making capacity.
2. National Examples & Review: Jamaica's Mental Health Act provides ordinary and emergency application routes (sections 6 and 8), and examination within 72 hours after compulsory admission under section 6 (section 10). Guyana uses the Mental Health Protection and Promotion Act 2022, in operation from 6 November 2023, with review/appeal safeguards. Use the applicable national forms and review limits; do not assume a universal physician-issued “72-hour hold”.
3. Lethal Means Restriction & Safety Planning: In outpatient practice, lethal means restriction is the single most effective public health suicide prevention strategy. Clinicians must actively collaborate with families to lock away agricultural pesticides, remove firearms, and dispense only limited 3- to 7-day supplies of medications that lack lethal cardiotoxicity in overdose (favoring SSRIs over TCAs).