Comprehensive Clinical Reference for Medical Professionals — Updated 2026
First-line treatment for major depressive disorder (MDD) and anxiety disorders worldwide. SSRIs account for 63.3% of all antidepressant use in Poland (IQVIA, 2018).
| Parameter | Details |
|---|---|
| ATC Code | N06AB10 |
| Mechanism | Selective SERT inhibition; S-enantiomer of citalopram. Higher SERT selectivity than citalopram, less 5-HT3 antagonism and hERG blockade. |
| Starting Dose | 10 mg/day PO |
| Therapeutic Range | 10–20 mg/day |
| Maximum Dose | 20 mg/day (10 mg/day in hepatic impairment, elderly) |
| Half-life | ~27-32 hours (allows once-daily dosing, minimal withdrawal) |
| Metabolism | CYP2C19 (major), CYP3A4, CYP2D6 (minor) |
| Key Brand Names (PL) | Cipralex (Lundbeck), Lex, Escitalopram HEXAL, Escitalopram Sandoz, Elicea, Estalice, Seroplex, Cipralex Generic: escitalopram (multiple manufacturers) |
| Reimbursement (NFZ) | Refundable at 85% (100% for selected indications — see NFZ list) |
| Efficacy | Among the most efficacious SSRIs in head-to-head meta-analyses (Cipriani et al., Lancet 2009). Superior tolerability to paroxetine and venlafaxine. |
| Side Effects | Nausea (common initially), headache, insomnia/drowsiness, sexual dysfunction (~30-40%), QTc prolongation (dose-dependent, less than citalopram above 20 mg) |
| Contraindications | Concurrent MAOI (14-day washout required, 5 weeks after fluoxetine), known hypersensitivity, concurrent pimozide |
| Special Populations | Hepatic impairment: max 10 mg/day. Elderly: consider 10 mg max. Renal: no dose adjustment typically needed. |
| Drug Interactions | CYP2C19 inhibitors (fluvoxamine, omeprazole) — increase levels. Strong CYP2D6 inhibitors — modest increase. Low risk of pharmacokinetic interactions vs. other SSRIs. |
| Discontinuation | Mild withdrawal syndrome possible (shorter half-life than fluoxetine but longer than paroxetine). Taper over 2-4 weeks. |
| Parameter | Details |
|---|---|
| ATC Code | N06AB06 |
| Mechanism | Selective SERT inhibition; weak dopamine reuptake inhibition at higher doses |
| Starting Dose | 50 mg/day PO |
| Therapeutic Range | 50–200 mg/day |
| Maximum Dose | 200 mg/day |
| Half-life | ~26 hours (active metabolite desmethylsertraline: ~62-104 hours) |
| Metabolism | CYP2B6 (major), CYP2C19, CYP2C9, CYP2D6, CYP3A4 |
| Key Brand Names (PL) | Zoloft (Pfizer), Sertralina BIOLAB, Sertralina ACHPHARMA, Sertralina Sandoz, Sertralina WZF, Zestra, Sertralin FARMED, Sertralina LEX |
| Reimbursement (NFZ) | Refundable at 85% for depression, OCD, PTSD, panic disorder |
| Efficacy | Among the most efficacious SSRIs (Cipriani et al., Lancet 2009). Broadest indication profile. Effective for MDD, OCD, PTSD, panic disorder, social anxiety disorder, PMDD. |
| Side Effects | Digestive: diarrhea (dose-dependent, common), nausea. Sexual dysfunction, insomnia, tremor. Less weight gain than paroxetine, less QTc concern than citalopram. |
| Contraindications | Concurrent MAOI, concurrent pimozide |
| Special Populations | Post-MI depression: sertraline is the preferred SSRI (SADHART trial). Hepatic impairment: start 25-50 mg, titrate slowly. |
| Drug Interactions | Minimal CYP2D6 inhibition (unlike paroxetine/fluoxetine). Moderate inhibitor of CYP2B6. Caution with drugs metabolised by CYP2C19. |
| Parameter | Details |
|---|---|
| ATC Code | N06AB04 |
| Mechanism | Selective SERT inhibition (racemic mixture of escitalopram + R-enantiomer) |
| Starting Dose | 20 mg/day PO |
| Therapeutic Range | 20–40 mg/day |
| Maximum Dose | 20 mg/day in elderly (>65 years), hepatic impairment; 40 mg/day in others |
| Half-life | ~35 hours (R-enantiomer accumulates) |
| Metabolism | CYP2C19, CYP3A4, CYP2D6 |
| Key Brand Names (PL) | Cipramil (Lundbeck), Citalopram HEXAL, Citalopram Sandoz, Citalopram WZF, Cipramil |
| Reimbursement (NFZ) | Refundable for depressive episodes |
| Efficacy | Comparable efficacy to other SSRIs. Slightly less potent than escitalopram. Fewest approved indications among SSRIs. |
| Side Effects | QTc prolongation (dose-dependent, EMA restriction above 40 mg/day), nausea, sweating, sexual dysfunction. |
| Contraindications | QTc >500 ms, concurrent QTc-prolonging drugs, recent MI, uncompensated heart failure |
| Drug Interactions | CYP2C19 inhibitors increase levels. Avoid with strong CYP2C19/2D6 inhibitors. Monitor QTc with other QTc-prolonging agents. |
| Parameter | Details |
|---|---|
| ATC Code | N06AB03 |
| Mechanism | Selective SERT inhibition |
| Starting Dose | 20 mg/day PO |
| Therapeutic Range | 20–80 mg/day |
| Maximum Dose | 80 mg/day |
| Half-life | ~1-3 days (parent); active metabolite norfluoxetine: ~7-15 days — longest among SSRIs |
| Metabolism | CYP2D6 (major), CYP2C9, CYP2C19, CYP3A4 |
| Key Brand Names (PL) | Prozac (Eli Lilly), Fluoksetyna ACHPHARMA, Fluoksetyna WZF, Fluoxetin, Pruval |
| Reimbursement (NFZ) | Refundable for MDD, bulimia nervosa, OCD |
| Efficacy | Robust evidence across age groups. First-line for MDD in adolescents. Activating profile (may worsen anxiety initially). |
| Side Effects | Activation/insomnia (common), nausea, anorexia, weight loss (early). Least weight gain among SSRIs long-term. Sexual dysfunction. |
| Drug Interactions | Strong CYP2D6 inhibitor (like paroxetine). Major interactions with tamoxifen, thioridazine, pimozide, TCAs, tramadol, warfarin. Long washout required before MAOI (5 weeks). |
| Special Advantages | Long half-life = minimal withdrawal symptoms, forgiving with missed doses. Preferred in patients with adherence concerns. |
| Parameter | Details |
|---|---|
| ATC Code | N06AB05 |
| Mechanism | Selective SERT inhibition; also 5-HT1A antagonist and mild anticholinergic |
| Starting Dose | 20 mg/day PO (SR: 25 mg/day) |
| Therapeutic Range | 20–50 mg/day (IR); 25–62.5 mg/day (SR) |
| Maximum Dose | 50 mg/day (IR); 62.5 mg/day (SR) |
| Half-life | ~21 hours (shorter than fluoxetine/escitalopram) |
| Metabolism | CYP2D6 (major, polymorphic — poor metabolisers ~7% of Europeans) |
| Key Brand Names (PL) | Seroxat (GlaxoSmithKline), Paroksetyna ACHPHARMA, Paroksetyna Sandoz, Paroksetyna WZF, Paroksetyna BIOLAB, Seroxat CR |
| Reimbursement (NFZ) | Refundable for MDD, panic disorder, social anxiety, GAD, PTSD |
| Efficacy | Comparable efficacy. Broad anxiety indication profile. High anticholinergic activity may provide benefit in anxious depression. |
| Side Effects | Sedation, weight gain (highest among SSRIs), anticholinergic effects, sexual dysfunction (highest rates). Discontinuation syndrome among the most severe of all SSRIs. |
| Contraindications | Concurrent MAOI, linezolid, thioridazine. Use caution in glaucoma, seizure disorders. |
| Drug Interactions | Strong CYP2D6 inhibitor. Significantly increases levels of TCAs, metoprolol, perphenazine, risperidone. CYP3A4 substrate. |
| Discontinuation | Severe discontinuation syndrome common: dizziness, "brain zaps," nausea, irritability. Requires slow taper (over 4-8+ weeks). |
| Parameter | Details |
|---|---|
| ATC Code | N06AB08 |
| Mechanism | Selective SERT inhibition; also 5-HT2A antagonist |
| Starting Dose | 50 mg/day PO (usually evening) |
| Therapeutic Range | 100–300 mg/day |
| Maximum Dose | 300 mg/day |
| Half-life | ~15-22 hours |
| Metabolism | CYP1A2 (major), CYP2C19, CYP2D6 |
| Key Brand Names (PL) | Faverin (Abbott), Fluvoxamine Actavis, Fluvoxamin WZF, Fluvoxamine Teva, Lyxum |
| Reimbursement (NFZ) | Refundable for OCD, MDD |
| Efficacy | First-line for OCD. Effective for MDD and social anxiety disorder. Less commonly prescribed in Poland vs. sertraline/escitalopram. |
| Side Effects | Sedation (more than other SSRIs), nausea, gastrointestinal effects. Less sexual dysfunction than paroxetine/fluoxetine. Agranulocytosis (rare). |
| Drug Interactions | Strong CYP1A2 inhibitor (significant). Inhibits CYP2C19, CYP3A4. Major interactions with theophylline, tizanidine, clozapine, carbamazepine, warfarin. Smoking induction of CYP1A2 may reduce efficacy. |
| Parameter | Details |
|---|---|
| ATC Code | N06AX16 |
| Mechanism | Dual SERT/NET inhibition. Serotonin reuptake inhibition at lower doses; norepinephrine reuptake inhibition emerges at higher doses. Also weak 5-HT2A, 5-HT1D antagonism and 5-HT3 antagonism. |
| Starting Dose | 75 mg/day (XR) PO, may split or once daily |
| Therapeutic Range | 75–225 mg/day (XR) |
| Maximum Dose | 375 mg/day (some evidence of increasing efficacy up to 375 mg) |
| Half-life | ~5 hours (parent); active metabolite O-desmethylvenlafaxine (ODV): ~11 hours |
| Metabolism | CYP2D6 (major, polymorphic) to ODV; CYP2C19, CYP3A4 |
| Key Brand Names (PL) | Effexor (Pfizer), Effexor XR, Venlafaxine HEXAL, Venlafaxine Sandoz, Venlafaxine WZF, Venlaksin, Efexor Retard |
| Reimbursement (NFZ) | Refundable for MDD, panic disorder, social anxiety disorder, GAD |
| Efficacy | Comparable to SSRIs for MDD. Superior in severe depression. High efficacy in TRD — most common 2nd-line choice in Poland after SSRI failure. |
| Side Effects | Dose-dependent hypertension (monitor BP at 3-6 weeks and periodically). Nausea, sweating, dry mouth, insomnia, sexual dysfunction. Discontinuation syndrome is severe (short half-life). |
| Drug Interactions | CYP2D6 substrate. Dose adjustment in poor metabolisers. Monitor BP with sympathomimetics. Risk of serotonin syndrome with other serotonergic drugs. |
| Monitoring | Blood pressure (especially at dose escalation), pulse, weight. Consider ECG if cardiac history. |
| Parameter | Details |
|---|---|
| ATC Code | N06AX21 |
| Mechanism | Dual SERT/NET inhibition. Also 5-HT2A antagonist. |
| Starting Dose | 30 mg/day (XR) PO, may increase to 60 mg/day after 1 week |
| Therapeutic Range | 30–60 mg/day (XR); up to 120 mg/day in some settings |
| Maximum Dose | 60 mg/day (standard); 120 mg/day (off-label in some jurisdictions) |
| Half-life | ~12 hours (XR formulation provides stable levels) |
| Metabolism | CYP2D6 (major), CYP1A2 (secondary) |
| Key Brand Names (PL) | Cymbalta (Eli Lilly), Duloksetyna BIOLAB, Duloksetyna HEXAL, Duloksetyna Sandoz, Duloksetyna WZF, Duloksetyna Actavis, Dulsena |
| Reimbursement (NFZ) | Refundable for MDD, diabetic peripheral neuropathy, chronic musculoskeletal pain |
| Efficacy | Comparable to venlafaxine. Dual indication (MDD + pain) — uniquely positioned for patients with comorbid chronic pain. FDA-approved for depression, GAD, diabetic neuropathy, fibromyalgia, chronic musculoskeletal pain. |
| Side Effects | Nausea (very common at start — take with food), dry mouth, constipation, fatigue, sweating, sexual dysfunction, dose-dependent BP increases. Hepatotoxicity risk (rare but serious). |
| Contraindications | Uncontrolled narrow-angle glaucoma, hepatic impairment (cirrhosis), severe renal impairment, concurrent MAOI, uncontrolled hypertension, heavy alcohol use |
| Monitoring | LFTs at baseline and periodically. BP monitoring. Hepatic function — discontinue if jaundice or significant transaminase elevation. |
| Parameter | Details |
|---|---|
| ATC Code | N06AX11 |
| Mechanism | Alpha-2 adrenergic autoreceptor and heteroreceptor antagonist — increases noradrenaline and serotonin release. Potent 5-HT2A, 5-HT2C, 5-HT3 antagonist. H1 histamine antagonist. |
| Starting Dose | 15 mg/day PO (evening) |
| Therapeutic Range | 15–45 mg/day |
| Maximum Dose | 45 mg/day |
| Half-life | ~20-40 hours |
| Metabolism | CYP1A2, CYP2D6, CYP3A4 |
| Key Brand Names (PL) | Remeron (Merck), Mirtazapina WZF, Mirtazapina Sandoz, Mirtazapina HEXAL, Mirtazapina ACHPHARMA, Mirtazapina BIOLAB, Remeron OD, Mirtasen |
| Reimbursement (NFZ) | Refundable for depressive episodes |
| Efficacy | Comparable efficacy to SSRIs. Particularly useful for depression with insomnia, anxiety, weight loss. Rapid onset of sleep improvement (often first night). |
| Side Effects | Sedation (strongest at lower doses — paradoxical), increased appetite/weight gain (significant), dry mouth, constipation. LOW sexual dysfunction risk. LOW serotonin syndrome risk. Agranulocytosis (rare: ~1-2 per million). |
| Special Advantages | No sexual dysfunction. Promotes weight gain (beneficial in cachexia). Antiemetic (5-HT3 antagonism). Anti-anxiety. Effective in TRD (often combined with SSRI — "California rocket fuel": mirtazapine + venlafaxine). |
| Drug Interactions | Moderate CYP3A4 inhibitor. CYP1A2/CYP2D6/CYP3A4 substrates may have increased levels. Additive CNS depression with benzodiazepines, opioids, alcohol. |
| Parameter | Details |
|---|---|
| ATC Code | N06AX12 |
| Mechanism | Norepinephrine-dopamine reuptake inhibitor (NDRI). Weak nicotinic acetylcholine receptor antagonist. |
| Starting Dose | 150 mg/day (SR) or XL PO |
| Therapeutic Range | 150–400 mg/day |
| Maximum Dose | 450 mg/day (XL) |
| Half-life | ~21 hours (parent); active hydroxybupropion: ~20 hours |
| Metabolism | CYP2B6 (major) |
| Key Brand Names (PL) | Availability limited — generic bupropion may be available through special import. Not widely marketed in Poland compared to EU peers. |
| Efficacy | Effective for MDD. Also approved for smoking cessation (Zyban). Less effective for anxiety disorders. Useful in TRD (augmentation strategy). |
| Side Effects | Activating (insomnia, agitation, anxiety — avoid in anxiety-predominant depression). LOW sexual dysfunction. Weight-neutral or mild weight loss. Dose-related seizure risk (0.4% at 450 mg/day; contraindicated in seizure risk). |
| Contraindications | Seizure disorders, eating disorders (bulimia/anorexia), MAOI use, abrupt alcohol/sedative withdrawal |
| Special Advantages | "Happy-Horny-Skinny" mnemonic: improves mood, no sexual dysfunction, weight-neutral/negative. No serotonin syndrome risk. |
| Parameter | Details |
|---|---|
| ATC Code | N06AX29 |
| Mechanism | SSRI (SERT inhibition) plus 5-HT1A agonist, 5-HT1B partial agonist, 5-HT3/5-HT1D/5-HT7 antagonist. Multimodal mechanism. |
| Starting Dose | 10 mg/day PO |
| Therapeutic Range | 5–20 mg/day |
| Maximum Dose | 20 mg/day |
| Half-life | ~66 hours |
| Metabolism | CYP2D6 (major), CYP3A4, CYP2C9/19, CYP2C19 |
| Key Brand Names (PL) | Brintellix (now Trintellix in some markets) (Lundbeck), Vortioxetine Sandoz, Vortioxetine HEXAL |
| Reimbursement (NFZ) | Refundable for MDD |
| Efficacy | Comparable to other SSRIs for core depressive symptoms. Superior cognitive function improvement (processing speed, attention, executive function) — unique among antidepressants. Meta-analyses support cognitive benefits. |
| Side Effects | Nausea (most common — dose-dependent, reduce dose if needed), headache, constipation, dry mouth. Lower sexual dysfunction than classic SSRIs (but not absent). Lower weight gain. |
| Drug Interactions | Strong CYP2D6 inhibitors increase vortioxetine levels substantially (reduce dose). CYP2D6 poor metabolisers: use half the standard dose. Avoid with MAOI. |
| Special Populations | Preferred in elderly (better cognitive profile, less orthostatic hypotension than venlafaxine). Low anticholinergic activity. |
| Parameter | Details |
|---|---|
| ATC Code | N06AX18 |
| Mechanism | Weak SERT inhibition, 5-HT2A antagonist, alpha-1 adrenergic antagonist, H1 antagonist. Active metabolite: mCPP (meta-chlorophenylpiperazine). |
| Starting Dose | 50 mg/day PO (evening) |
| Therapeutic Range | 150–400 mg/day (antidepressant); 25-100 mg/day (sleep) |
| Maximum Dose | 400 mg/day (inpatient); lower for outpatient |
| Half-life | ~5-9 hours (parent); mCPP: ~8 hours |
| Metabolism | CYP3A4 (major) |
| Key Brand Names (PL) | Trittico (IRG), Trazodona WZF, Trazodon Actavis, Trazodon Sandoz, Trittico DT, Trittico CR |
| Efficacy | Less commonly used as sole antidepressant in modern practice. Often used at low doses for insomnia comorbid with depression/anxiety. |
| Side Effects | Sedation (common), dry mouth, dizziness (orthostatic hypotension). Priapism (rare but medical emergency — alpha-1 blockade). Nausea. |
| Contraindications | Concurrent MAOI, recent MI, severe hepatic/renal impairment |
| Parameter | Details |
|---|---|
| ATC Code | N06AX15 |
| Mechanism | MT1/MT2 melatonin receptor agonist + 5-HT2C antagonist. Regulates circadian rhythm. |
| Starting Dose | 25 mg/day PO (evening) |
| Therapeutic Range | 25 mg/day (may increase after 2-4 weeks if needed) |
| Half-life | ~1-2 hours (rapid clearance) |
| Metabolism | CYP1A2 (major) |
| Key Brand Names (PL) | Valdoxan (Servier), Agomelatyna WZF, Agomelatyna Sandoz |
| Reimbursement (NFZ) | Refundable for MDD |
| Efficacy | Effective for MDD, particularly with sleep/circadian disturbance. Less robust evidence base than SSRIs. Superior sleep quality improvement. |
| Side Effects | Nausea, headache, dizziness. LOW sexual dysfunction. LOW weight gain. LOW discontinuation syndrome. |
| Contraindications | Hepatic impairment (hepatotoxicity risk — monitor LFTs), concurrent fluvoxamine (CYP1A2 inhibitor). |
| Monitoring | LFTs at baseline, 6 weeks, 12 weeks, 24 weeks. Discontinue if ALT >3x ULN. |
TCAs are the most dangerous antidepressants in overdose due to cardiac sodium channel blockade causing lethal arrhythmias and QRS widening. Use with caution in patients with suicide risk. Baseline ECG recommended before initiation.
| Parameter | Details |
|---|---|
| ATC Code | N06AA09 |
| Mechanism | Non-selective SERT/NET inhibition. Also muscarinic, H1, alpha-1 adrenergic antagonist. |
| Starting Dose | 25-50 mg/day PO (evening) |
| Therapeutic Range | 75–150 mg/day |
| Maximum Dose | 150 mg/day (outpatient); 300 mg/day (inpatient) |
| Half-life | ~10-50 hours (high inter-individual variability) |
| Metabolism | CYP2D6, CYP2C19, CYP1A2 — active metabolite nortriptyline |
| Key Brand Names (PL) | Amitriptylina WZF, Amitriptylina Sandoz, Amitriptylina HEXAL, Syntamin, Sarotena |
| Reimbursement (NFZ) | Refundable for depressive episodes |
| Uses Beyond MDD | Chronic pain, neuropathic pain, migraine prophylaxis, tension-type headache, fibromyalgia, nocturnal enuresis (children). Low-dose (10-75 mg) frequently used for pain syndromes. |
| Side Effects | Sedation (strong), anticholinergic (dry mouth, blurred vision, urinary retention, constipation), orthostatic hypotension (alpha-1 blockade), weight gain, cardiac effects (QTc prolongation, arrhythmias). |
| Parameter | Details |
|---|---|
| ATC Code | N06AA02 |
| Mechanism | Most potent SERT inhibitor among TCAs. Also NET inhibition. |
| Starting Dose | 25 mg/day PO, increase gradually |
| Therapeutic Range | 75–250 mg/day |
| Maximum Dose | 250 mg/day |
| Half-life | ~18-46 hours (active metabolite desmethylclomipramine: ~23-57 hours) |
| Metabolism | CYP2D6, CYP1A2 |
| Key Brand Names (PL) | Anafranil (Novartis), Klomipramina WZF, Klomipramina Sandoz |
| Efficacy | Most efficacious TCA for OCD. May be slightly more efficacious than other TCAs for MDD but worse tolerability. |
| Side Effects | Strongest anticholinergic effects among TCAs. Seizure risk at higher doses. Sexual dysfunction. Sedation. |
| Parameter | Details |
|---|---|
| ATC Code | N06AA10 |
| Mechanism | NET > SERT inhibition. Active metabolite of amitriptyline. Fewer anticholinergic effects than amitriptyline. |
| Starting Dose | 25-50 mg/day PO |
| Therapeutic Range | 75–150 mg/day |
| Half-life | ~15-50 hours |
| Metabolism | CYP2D6 |
| Key Brand Names (PL) | Aventyl, Pamelor (less common in PL market), Nortryptyline |
| Advantages | Better tolerated than amitriptyline (less anticholinergic). Inverted U-shaped plasma response curve: therapeutic window 50-150 ng/mL. |
Irreversible MAOIs require strict dietary tyramine restriction and mandatory 14-day washout when switching to/from other antidepressants (5 weeks after fluoxetine). MAOIs are reserved for treatment-resistant/atypical depression.
| Parameter | Details |
|---|---|
| ATC Code | N06BG02 |
| Mechanism | Reversible inhibitor of MAO-A (RIMA). Selectively inhibits MAO-A (which metabolises serotonin, norepinephrine, dopamine) without affecting MAO-B. No tyramine restriction required (reversible binding). |
| Starting Dose | 300 mg/day PO (divided into 2-3 doses) |
| Therapeutic Range | 300–600 mg/day |
| Maximum Dose | 600 mg/day |
| Half-life | ~1 hour (short — multiple daily dosing) |
| Metabolism | Not significantly metabolised by CYP450 system. Low drug-interaction potential. |
| Key Brand Names (PL) | Aurorix (Roche), Moclobemidum, Manerix (less common) |
| Efficacy | Comparable to TCAs for MDD. Better tolerability. Particularly useful for atypical depression (mood reactivity, hyperphagia, hypersomnia, leaden paralysis, rejection sensitivity). |
| Side Effects | Insomnia (activating), nausea, dizziness. LOW sexual dysfunction. LOW anticholinergic effects. LOW discontinuation syndrome. |
| Advantages | No dietary tyramine restriction. Minimal drug interactions (not CYP metabolised). No orthostatic hypotension. Safe in cardiac disease. Can be combined with other antidepressants more safely than irreversible MAOIs. |
| Step | Strategy | Common Agents (Poland) |
|---|---|---|
| 1st line | SSRI monotherapy | Sertraline 50-200 mg/day or Escitalopram 10-20 mg/day |
| 2nd line | Switch to different SSRI or SNRI | Switch sertraline → venlafaxine or escitalopram → duloxetine |
| 3rd line | Augmentation or combination | Mirtazapine + SSRI/SNRI ("California rocket fuel"); atypical antipsychotic (quetiapine, aripiprazole) |
| 4th line | Ketamine/esketamine | Racemic ketamine (Polish standard, 2024); Spravato (esketamine nasal spray, NFZ-funded program B.147 for TRD) |
| 5th line | MAOI or ECT | Moclobemide; ECT for severe/refractory cases, especially with psychotic features or high suicide risk |
| Combination | Rationale | Evidence |
|---|---|---|
| SSRI/SNRI + Mirtazapine | Complementary mechanisms: SERT + alpha-2 antagonism + 5-HT2A antagonism | High. Remission ~50% in TRD (open-label trials). Known as "California rocket fuel." |
| SSRI/SNRI + Bupropion | Dual mechanism; may mitigate SSRI-induced sexual dysfunction and fatigue | Moderate. Effective augmentation strategy. "Welloft" (sertraline + bupropion) well-studied. |
| SSRI + Vortioxetine | SSRI blocks SERT; vortioxetine's multimodal actions add cognitive benefits | Emerging. Some evidence for enhanced cognitive improvement and response. |
| Antidepressant + Atypical antipsychotic | Augmentation with quetiapine, aripiprazole, or brexpiprazole | Strong. FDA/EMA-approved augmentation agents. Quetiapine XR most studied. |
| Predominant Symptoms | Preferred Agent | Rationale |
|---|---|---|
| Anxiety-predominant depression | Sertraline, Escitalopram, Paroxetine | Proven efficacy in GAD, panic, social anxiety comorbidity |
| Insomnia, low appetite, weight loss | Mirtazapine, Trazodone (low dose) | Sedating, appetite-stimulating |
| Fatigue, anhedonia, low energy | Bupropion, Venlafaxine, Fluoxetine | Activating profiles; NE/dopamine effects |
| Chronic pain comorbidity | Duloxetine, Venlafaxine, Amitriptyline, Nortriptyline | SNRI/TCA efficacy in neuropathic and musculoskeletal pain |
| Cognitive impairment | Vortioxetine, Bupropion | Documented cognitive enhancement |
| Sexual dysfunction concerns | Bupropion, Mirtazapine, Vortioxetine, Agomelatine | Minimal serotonergic sexual side effects |
| Weight gain concerns | Bupropion, Fluoxetine, Vortioxetine, Venlafaxine | Weight-neutral or weight loss |
| Poor adherence / frequent missed doses | Fluoxetine, Vortioxetine | Long half-life reduces withdrawal risk |
| Cardiac disease | Sertraline | SADHART trial: safe in post-MI patients. Avoid TCAs, citalopram (QTc). |
| Elderly patients | Sertraline, Escitalopram, Vortioxetine | Favorable side-effect profile, lower anticholinergic burden |
| From | To | Required Washout | Notes |
|---|---|---|---|
| Most SSRIs (sertraline, escitalopram, etc.) | MAOI (reversible or irreversible) | 14 days | Prevent serotonin syndrome |
| Fluoxetine | MAOI (any) | 5 weeks | Exception: exceptionally long half-life of norfluoxetine |
| MAOI | Most SSRIs/SNRIs | 14 days | Allow MAO enzyme regeneration |
| MAOI | Fluoxetine | 14 days | Then additional 5 weeks due to fluoxetine's long half-life |
| SSRI/SNRI | Another SSRI/SNRI | Varies (1-5 days) | Direct switch possible for most. Cross-taper recommended for paroxetine/venlafaxine (severe withdrawal). |
| Paroxetine | Another antidepressant | Cross-taper over 2-4 weeks | Severe discontinuation with abrupt stop |
| Venlafaxine | Another antidepressant | Cross-taper over 2-4 weeks | Short half-life, severe withdrawal |
| Drug | t1/2 (h) | CYP Enzymes | CYP Inhibition | Food Effect | Renal Dose Adj. |
|---|---|---|---|---|---|
| Escitalopram | 27-32 | 2C19, 3A4, 2D6 | Minimal | No | No |
| Sertraline | 26 (+62-104 active) | 2B6, 2C19, 2C9 | Mild 2D6, 2B6 | No | Moderate impairment: reduce dose |
| Citalopram | 35 | 2C19, 3A4, 2D6 | Mild 2C19, 2D6 | No | No |
| Fluoxetine | 1-3 (+7-15 norfluoxetine) | 2D6, 2C9, 2C19 | Strong 2D6 | No | Severe: avoid |
| Paroxetine | 21 | 2D6 (polymorphic) | Strong 2D6 | No | Moderate: reduce dose |
| Fluvoxamine | 15-22 | 1A2, 2C19, 2D6 | Strong 1A2, 2C19 | No | Severe: avoid |
| Venlafaxine | 5 (parent), 11 (ODV) | 2D6, 2C19, 3A4 | Minimal | Take with food (XR) | Severe: reduce dose |
| Duloxetine | ~12 | 2D6, 1A2 | Mild 2D6 | Take with food | Severe: avoid |
| Mirtazapine | 20-40 | 1A2, 2D6, 3A4 | Moderate 3A4 | No | Severe: reduce dose |
| Bupropion | ~21 (+21 OH) | 2B6 | 2B6 inhibitor | No | Severe: reduce dose |
| Vortioxetine | ~66 | 2D6, 3A4, 2C9/19 | Minimal | No | Mild: no adjustment |
| Trazodone | 5-9 | 3A4 | Minimal | No | Severe: reduce dose |
| Agomelatine | 1-2 | 1A2 | None | Take without food | Mild: no adjustment |
| Amitriptyline | 10-50 | 2D6, 2C19, 1A2 | 2D6, 2C19 | No | Severe: avoid |
| Moclobemide | ~1 | Not CYP-dependent | None | Take 30 min before meals | Moderate: reduce dose |
This document was compiled from publicly available scientific sources and official registries. It is provided for educational purposes for medical professionals. Always verify with current official SmPC documentation and NFZ regulations. Last updated: September 2026.