Direct questioning about suicide does not increase suicidal ideation — this is supported by systematic reviews including a Cochrane review (Dazzi et al. 2014) which found no evidence that asking about suicidal thoughts causes or increases suicidal behaviour. The myth that asking "plants the idea" is one of the most damaging misconceptions in clinical practice and leads to under-assessment of suicide risk. Direct questioning within a therapeutic relationship relieves distress, opens dialogue, and is the first step in risk reduction. The clinical documentation of a suicide risk assessment is a medicolegal imperative — it must include: what was asked, the patient's response, identified risk factors (alcohol, isolation, access to means, previous attempts, male sex, chronic pain), protective factors (family support, religious beliefs, help-seeking behaviour), and the clinical decision made. The bipolar red flag before prescribing SSRIs is critical — antidepressants prescribed as monotherapy in bipolar disorder (particularly bipolar II, which is frequently misdiagnosed as recurrent unipolar depression) can precipitate hypomanic or manic episodes, trigger mixed states, and cause rapid cycling. The MDQ (Mood Disorder Questionnaire) is a validated 13-item screening tool that takes 5 minutes to complete — a score of ≥7 with functional impairment has 73% sensitivity for bipolar I disorder. In any patient with multiple previous depressive episodes not responding to antidepressants, a bipolar screen should be performed before prescribing a further course of antidepressant monotherapy. Postnatal depression affects 10–15% of mothers in the UK and is the most under-diagnosed condition in perinatal care — the EPDS is validated for use in primary care and should be administered at 6-week postnatal review and again at 3–4 months. An EPDS score ≥13, or any score on the question about self-harm (question 10), warrants urgent assessment and referral.

The PHQ-9 is the most widely validated and widely used depression outcome measure in UK primary care — it was developed and validated against DSM-IV criteria for major depressive disorder (Kroenke et al. JGIM 2001) and has been extensively validated in UK populations. Its value is not just in initial classification (which can be done clinically) but in serial outcome measurement — a 5-point drop in PHQ-9 score represents a clinically meaningful response, and a score below 10 at 8–12 weeks represents remission. NICE NG222 (Depression in Adults, 2022) specifically recommends using a validated outcome tool (PHQ-9 or equivalent) at every contact to monitor treatment response, rather than relying solely on clinical impression. Serial PHQ-9 documentation also provides clear medicolegal evidence of clinical decision-making at each escalation point. The DSM-5 distinction between "adjustment disorder with depressed mood" (low mood as a proportionate response to an identifiable stressor, resolving within 6 months of stressor removal) and "major depressive disorder" (meets full diagnostic criteria regardless of precipitant) has treatment implications — adjustment disorder is primarily managed with psychological support and watchful waiting, whereas major depressive disorder needs structured psychological therapy ± antidepressant regardless of whether a stressor precipitated it. The stressor does not determine the diagnosis — the symptom severity and duration do. The PHQ-9 score at the functional impairment question is particularly useful in GP practice — "How difficult have these problems made it for you to do your work, take care of things at home, or get along with other people?" — as it directly assesses the impact threshold that determines management decisions.

The investigation of organic causes of low mood is not optional — it is a core component of every depression assessment. NICE NG222 recommends a minimum screen of: TSH, FBC, ferritin, B12/folate, HbA1c, and U&E in patients presenting with low mood, to exclude reversible causes before initiating antidepressants. The cost of missing hypothyroidism as the cause of low mood is significant — a patient may be on antidepressants for years, with partial response, when the underlying thyroid disorder continues. TSH is the single most sensitive and specific test for thyroid dysfunction and should be checked routinely. The relationship between hormonal contraception and low mood is clinically important and generates significant patient-GP consultation — a large Danish cohort study (Skovlund et al. JAMA Psychiatry 2016, n=1 million) found that hormonal contraception use was associated with a 20–40% increased risk of first antidepressant prescription and first depression diagnosis. The progestogen-only pill had the highest associated risk. The mechanism involves progestogen downregulation of GABA-A receptors (similar to premenstrual dysphoric disorder pathophysiology). GPs should review hormonal contraception method in women presenting with low mood that temporally correlates with contraceptive initiation or change. Alcohol is the most common modifiable cause of persistent depression in primary care — heavy drinkers who successfully reduce alcohol often experience dramatic mood improvement within weeks without any antidepressant. Treating depression with SSRIs without addressing alcohol misuse has poor outcomes — alcohol reduces SSRI efficacy and increases impulsivity and suicide risk. The sequence should be: screen (AUDIT-C), brief intervention, and alcohol reduction before or concurrent with antidepressant initiation.

The sodium baseline before starting SSRIs is a patient safety imperative that is frequently overlooked — SSRIs and SNRIs cause SIADH (syndrome of inappropriate antidiuretic hormone secretion) in approximately 1–5% of patients, causing hyponatraemia. Risk factors include: older age (>65), female sex, low BMI, concurrent diuretic use, pre-existing hyponatraemia, and renal impairment. Severe hyponatraemia from SSRIs (sodium <125 mmol/L) can cause confusion, seizures, coma, and death. A baseline sodium is mandatory before prescribing an SSRI in any patient over 65 or on diuretics. Repeat sodium at 2–4 weeks after starting (before reaching steady state). The ECG before citalopram or escitalopram is a BNF and MHRA requirement — both drugs cause dose-dependent QTc prolongation, with citalopram being the most potent QTc-prolonging SSRI. Maximum dose of citalopram in patients aged ≥65 is 20 mg (not 40 mg). Maximum dose in all adults if QTc >450 ms in men or >460 ms in women = avoid citalopram/escitalopram, use sertraline instead. Adverse Childhood Experiences (ACEs) are strongly and dose-dependently associated with adult mental illness — patients with ≥4 ACEs have a 4.5-fold increased risk of depression. Identifying ACEs in the social history guides treatment (trauma-focused CBT, EMDR) and explains why standard SSRI + CBT may have limited effect in patients with complex trauma backgrounds. Screening for domestic violence with a validated tool (DASH — Domestic Abuse, Stalking and Honour-Based Violence questionnaire) is part of a comprehensive depression assessment — coercive control and intimate partner violence are among the strongest environmental drivers of depression in women and should be actively asked about.

NICE NG222 (Depression in Adults, 2022) represented a significant shift in the recommended treatment pathway — the previous stepped care model was replaced with a more individualised, shared-decision-making approach that treats all types of interventions (pharmacological, psychological, social) as co-equal options rather than hierarchical steps. Key changes: (1) SSRIs are no longer automatically recommended as first-line over psychological therapy — the patient's preference is central; (2) the recommendation against prescribing antidepressants for mild depression remains — watchful waiting and low-intensity psychological intervention are preferred; (3) exercise is explicitly recommended as a treatment for mild-moderate depression (not just lifestyle advice); (4) social prescribing is explicitly included in the treatment pathway for the first time. The NHS Talking Therapies (formerly IAPT — Improving Access to Psychological Therapies) service is the primary referral destination for mild-moderate depression — it is the largest mental health programme in the world and is available in every CCG/ICB area in England. Self-referral is possible (the patient does not need a GP referral letter). Current NHS targets require that 75% of patients completing treatment achieve reliable improvement and 50% recover to below clinical caseness. GPs should know their local Talking Therapies service access number and waiting time. Mindfulness-Based Cognitive Therapy (MBCT) has NICE recommendation specifically for relapse prevention — not for the acute depressive episode, but for patients in remission who have had 3 or more previous depressive episodes. The NNT for MBCT preventing relapse at 12 months is approximately 4 (compared to antidepressant continuation), making it one of the most evidence-based psychological interventions in psychiatry.

Sertraline as the preferred first-line SSRI for most adults is consistent with NICE NG222, the Cipriani et al. network meta-analysis (Lancet 2018 — the largest antidepressant RCT network meta-analysis, 522 trials, 116,000 patients), and the BNF prescribing guidance. Sertraline and escitalopram ranked highest for efficacy in the Cipriani meta-analysis; sertraline was the recommended first-line choice based on its combination of efficacy, safety, and cost-effectiveness. The minimum adequate trial of an antidepressant is 4 weeks at therapeutic dose — below this, it is not possible to assess treatment response. Patients who stop antidepressants within 2–4 weeks due to initial side effects (nausea, headache, sleep disturbance — common and transient) should be counselled that side effects typically resolve within 1–2 weeks and the therapeutic effect is yet to develop. The prescribing consultation should explicitly state: "You may feel slightly worse before you feel better in the first 1–2 weeks — this is normal and does not mean the medication is wrong for you." Mirtazapine's pharmacological profile (H1 antagonism — sedation/appetite; alpha-2 antagonism — increases noradrenaline and serotonin release; 5-HT2 and 5-HT3 antagonism — reduces anxiety and GI side effects) makes it clinically useful in a specific phenotype of depression: older patient, marked insomnia, weight loss, poor appetite, anxious. These patients often respond poorly to activating SSRIs (agitation, worsened insomnia) and better to mirtazapine's sedating profile. The well-known "paradox" is that mirtazapine is less sedating at 30–45 mg than at 15 mg — the noradrenergic activation at higher doses counteracts the antihistamine sedation. Duloxetine as the first-line choice for depression + diabetic neuropathic pain simplifies prescribing — rather than an SSRI + pregabalin/amitriptyline, duloxetine addresses both conditions with one agent at one dose.

The 6-month post-remission continuation rule is one of the most important and most violated principles in GP prescribing for depression — the discontinuation rate within the first 3 months of treatment is approximately 40–50% in primary care, meaning nearly half of all patients stop their antidepressant before any meaningful therapeutic effect can be established, let alone before the post-remission maintenance period. The primary reason patients stop early is a misunderstanding of the treatment paradigm — many patients assume antidepressants are a short-term intervention, like antibiotics, and stop when they "feel better." The prescribing consultation must address this explicitly: "The medication needs to continue for at least 6 months after you feel well — feeling better is when we're treating the risk of the depression coming back, not when we stop." Antidepressant discontinuation syndrome is clinically significant and was significantly underestimated until the Royal College of Psychiatrists published their landmark guidance (Davies and Read 2019, Addictive Behaviours) which found that withdrawal symptoms were reported by 56% of antidepressant users, with 46% describing them as severe. The FINISH mnemonic (Flu-like, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal) is the standard teaching tool. Paroxetine is the most problematic SSRI for discontinuation (shortest half-life → steepest plasma level drop), followed by venlafaxine. Fluoxetine has the longest half-life and effectively self-tapers. Providing patients with a written tapering schedule (available from the RCPsych website) and warning them in advance that they may experience discontinuation symptoms is both clinically important and a patient safety issue that reduces unnecessary GP re-consultations and emergency attendances.

The evidence base for exercise as a treatment for depression is substantial and underutilised — a 2023 network meta-analysis (Noetel et al. BMJ 2024, 218 RCTs, 14,170 participants) concluded that walking/jogging, yoga, strength training, and mixed aerobic exercise were all effective treatments for depression, with effect sizes comparable to antidepressants and psychotherapy. The key issue in primary care is that exercise is often mentioned as lifestyle advice (one-liner at the end of the consultation) rather than prescribed as a structured intervention with specificity (modality, frequency, duration, intensity, referral mechanism). NICE NG222 is explicit that GPs should discuss and support physical activity as a treatment option, not just mention it. Referring to the NHS exercise referral scheme (available through most practices) with a specific activity prescription has significantly better outcomes than verbal advice alone. The CBT-I (Cognitive Behavioural Therapy for Insomnia) is clinically superior to any pharmacological sleep aid for chronic insomnia — multiple RCTs and meta-analyses show CBT-I produces larger and more durable improvements in sleep onset latency, total sleep time, and sleep quality than benzodiazepines or Z-drugs, without the risks of dependence, tolerance, or next-day sedation. NHS Sleepio is a digital CBT-I programme available free on the NHS in England (via self-referral online) and has been shown in RCTs to be as effective as face-to-face CBT-I. Given the profound bidirectional relationship between sleep and depression, offering CBT-I (via Sleepio or IAPT) to every depressed patient with insomnia is evidence-based standard of care, not an optional extra.

The 2-week review after starting an antidepressant is a patient safety requirement, not a convenience. The MHRA issued a warning in 2004 (following concerns from the CSM) that SSRIs and SNRIs may be associated with an increased risk of suicidal thoughts and self-harm in the early weeks of treatment, particularly in younger patients (under 30). The mechanism is thought to involve increased psychomotor activation (the patient feels more energised and able to act on passive suicidal ideation before the antidepressant's mood-lifting effect has developed). For this reason, a face-to-face or telephone review at 2 weeks is the minimum standard — this is documented in the BNF, NICE NG222, and multiple RCGP guidelines. Patients should also be given an emergency contact number for the interim period. The sexual dysfunction side effects of SSRIs are significantly underreported and underasked — studies show 30–40% of patients on SSRIs experience sexual dysfunction (reduced libido, delayed orgasm, anorgasmia, erectile dysfunction), but fewer than 20% spontaneously report it because of embarrassment. GPs must ask directly: "Some people find this medication affects their sexual desire or function — has that been an issue for you?" This is particularly important in younger patients for whom sexual dysfunction may be a deal-breaker for continued treatment. Switching to mirtazapine, bupropion (off-label in UK), or agomelatine substantially reduces sexual side effects while maintaining antidepressant efficacy. The SSRI-bone density association requires long-term monitoring — observational studies show that SSRIs reduce bone mineral density through serotonin receptor-mediated effects on osteoblast and osteoclast activity. After 5 years of SSRI use, the fracture risk increase is clinically significant (similar magnitude to glucocorticoid-induced osteoporosis). DXA scan surveillance should be considered in postmenopausal women and men aged ≥70 on long-term SSRIs.