Depression (Major Depressive Disorder) — Causes, PHQ-9, SSRIs, CBT & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Major depressive disorder (MDD) is a common and serious mental health condition characterised by persistent low mood and/or loss of interest or pleasure (anhedonia), present for at least 2 weeks and causing significant impairment in work, relationships, and daily functioning. Depression is not a sign of weakness or a character flaw — it is a medical condition with biological, psychological, and social causes. It affects 280 million people globally and is the single leading cause of disability worldwide. Depression exists on a spectrum of severity: mild (5 core symptoms, minimal functional impairment); moderate (persistent symptoms, moderate impairment); severe (multiple symptoms including psychotic features, suicidal ideation, or significant functional impairment requiring specialist care). Dysthymia (persistent depressive disorder) is a milder but chronic form lasting 2 or more years.

Depression is caused by a complex interaction of biological, psychological, and social factors (biopsychosocial model). Biological: genetic factors account for approximately 40% of risk — no single 'depression gene'; serotonin (5-HT), dopamine, and noradrenaline neurotransmitter system dysregulation; HPA axis hyperactivity (elevated cortisol in chronic stress); neuroinflammation (elevated IL-6, TNF-alpha, CRP); hippocampal volume reduction (chronic stress impairs neurogenesis). Psychological risk factors: negative cognitive schemas (Beck's cognitive triad — negative view of self, world, and future); perfectionism; rumination; childhood adversity and trauma (abuse, neglect, loss of a parent); low self-esteem. Social risk factors: poverty, unemployment, social isolation, recent major life events (bereavement, divorce, job loss), chronic illness, caring responsibilities, housing insecurity, domestic abuse, discrimination, and loneliness. Medical comorbidities associated with depression: chronic pain, hypothyroidism, Parkinson's disease, cancer, diabetes, cardiovascular disease, traumatic brain injury, and postnatal period.

Core symptoms of major depression (DSM-5): depressed mood most of the day, nearly every day (sadness, emptiness, tearfulness — reported by patient or observed by others); markedly diminished interest or pleasure in all, or almost all, activities (anhedonia). Other symptoms: significant unintentional weight loss or gain (change over 5% of body weight); insomnia or hypersomnia; psychomotor agitation or retardation; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive guilt; difficulty thinking, concentrating, or making decisions ('brain fog'); recurrent thoughts of death, suicidal ideation, or suicide attempt. A diagnosis of MDD requires 5 or more symptoms (including at least one core symptom) present for 2 or more weeks. Additional features: somatic symptoms (headache, back pain, GI symptoms); diurnal variation (worse in the morning, gradually improving through the day — classic melancholic depression); psychotic features (hallucinations or delusions) in severe depression; anhedonia without sadness ('depressed without feeling depressed' — sometimes misidentified).

Clinical interview: thorough psychiatric history including symptom duration, severity, functional impact, past episodes, family history of depression/bipolar disorder, suicide risk assessment (SADPERSONS or Columbia Suicide Severity Rating Scale — CSSRS), substance use, and medical history. Validated screening tools: PHQ-9 (Patient Health Questionnaire-9) — 9 questions based on DSM-5 criteria; scored 0-27; mild 5-9, moderate 10-14, moderately severe 15-19, severe 20-27. PHQ-2 (2-item ultra-brief screener). HAM-D (Hamilton Depression Rating Scale). Blood tests to exclude organic causes: thyroid function (hypothyroidism), FBC (anaemia), renal and liver function, B12 and folate, blood glucose, inflammatory markers, calcium. Imaging: not routinely indicated; consider brain MRI in late-onset depression, focal neurological signs, or atypical features. Differentiate from bipolar disorder (essential — antidepressant monotherapy in bipolar disorder risks inducing mania): enquire about past manic or hypomanic episodes, family history of bipolar disorder, rapid cycling; consider MDQ (Mood Disorder Questionnaire) screening.

Stepped care model (NICE NG222, 2022): Step 1 (mild depression): psychoeducation, self-help resources, behavioural activation, structured physical activity prescription (Exercise for Depression — minimum 3 sessions/week for 45 minutes); guided self-help using CBT principles; online CBT (e.g., SilverCloud, Mood Gym). Step 2 (mild-moderate): IAPT (Improving Access to Psychological Therapies) — individual CBT (8-20 sessions) or interpersonal therapy (IPT); antidepressants if preferred or previous response. Step 3 (moderate-severe): antidepressant therapy + psychological therapy. SSRIs (first-line antidepressants): sertraline (50-200 mg — recommended first-line by NICE and WHO), escitalopram (10-20 mg — excellent tolerability), fluoxetine (20-60 mg — longest half-life, good for those with adherence issues), citalopram (20-40 mg), paroxetine (20-50 mg — more side effects). SNRIs: venlafaxine (75-225 mg — effective for depression and anxiety; hypertension monitoring required at higher doses), duloxetine (60-120 mg — also for chronic pain, diabetic neuropathy). Mirtazapine (15-45 mg — noradrenaline and specific serotonin antagonist; sedating, weight gain, effective for anxious/insomnia-prominent depression). All antidepressants take 4-6 weeks to show full effect — do not stop early. Combine antidepressant with psychological therapy for best outcomes in moderate-severe depression. Second-line and augmentation: adding lithium, atypical antipsychotics (quetiapine, aripiprazole), thyroid hormone, or second antidepressant. Treatment-resistant depression (TRD — failed 2 adequate antidepressant trials): esketamine (Spravato — intranasal, rapid-acting, approved for TRD and MDD with acute suicidal ideation); transcranial magnetic stimulation (TMS — repetitive TMS; non-invasive brain stimulation; approved for TRD); electroconvulsive therapy (ECT — gold standard for severe/treatment-resistant/psychotic depression; highly effective — 60-80% response rate). Psychotherapy: CBT, IPT, behavioural activation, EMDR (for PTSD-related depression), mindfulness-based cognitive therapy (MBCT — prevents relapse in recurrent depression; 3 or more previous episodes).

Untreated depression causes profound disability — more days of disability per year than most chronic physical conditions including diabetes, arthritis, and cardiovascular disease. Suicide risk: major depression carries a 6-15% lifetime risk of suicide — the 2nd leading cause of death in people aged 15-29 globally. Each year approximately 700,000 people die by suicide worldwide; 50-90% have a diagnosable mental illness (most commonly depression) at the time. Recurrence: 50% of people with a first episode will have a second; after 3 episodes, 90% will have further episodes without maintenance treatment. Untreated depression worsens physical health outcomes — it doubles the risk of cardiovascular disease mortality, worsens diabetes control (HbA1c), reduces immune function, and increases risk of dementia. Relationship breakdown, job loss, educational underachievement, and social isolation are significant functional consequences. Depression and anxiety frequently co-occur — each worsening the other if untreated.

Regular physical activity is the single most evidence-based lifestyle intervention for depression: 150 minutes/week of moderate aerobic exercise reduces depression risk by 35% and reduces severity of active depression. Social connection: loneliness and social isolation are major risk factors — maintain meaningful relationships and engage in community activities. Sleep hygiene: maintain regular sleep schedule; address insomnia (a major risk factor for depression recurrence) — CBT for insomnia (CBT-I) is recommended over sleeping tablets. Mindfulness-based cognitive therapy (MBCT): recommended by NICE for people with 3 or more previous episodes — reduces recurrence by 43%. Limit alcohol (a central nervous system depressant that worsens depression long-term). Diet: Mediterranean diet (fruits, vegetables, whole grains, fish, olive oil, legumes) is associated with 30-35% reduced depression risk (SMILES trial showed dietary intervention improved depression outcomes). Antidepressant maintenance for recurrent depression: continue antidepressants for at least 2 years after recovery from a second or subsequent episode. Do not stop antidepressants suddenly — taper slowly under GP or psychiatrist guidance to reduce discontinuation symptoms.

Call emergency services (999/911) or go to Emergency Department immediately if: you or someone you know is in immediate danger from suicidal thoughts, has made a suicide attempt, or has self-harmed; severe inability to care for yourself (not eating, not drinking, unable to get out of bed); severe psychotic symptoms (hallucinations, delusions) with depression; extreme agitation and risk to self or others. Contact your GP urgently, call 111, or attend mental health crisis team for: active suicidal thoughts without immediate intent — same-day or next-day assessment; significant worsening of depression on antidepressants (especially in first 2 weeks — SSRIs can occasionally increase agitation and suicidal ideation early in treatment — NICE recommends face-to-face follow-up at 1-2 weeks for those under 30 and those at risk); severe functional impairment — unable to work, maintain relationships, or activities of daily living. Useful crisis contacts: Samaritans 116 123 (UK — 24/7, free); SHOUT text 85258 (text-based crisis support, UK); Crisis Team via your GP or 111. See your GP routinely for: low mood persisting more than 2 weeks; loss of interest in activities you previously enjoyed; sleep or appetite disturbance with low mood; to discuss PHQ-9 assessment, talking therapies referral, or antidepressant treatment.