Antidepressants and mood stabilisers

• Antidepressants correct biased monoamine signalling in depression and several classes also treat anxiety, pain and insomnia. ^[3]
• For major depression of moderate or greater severity, the SSRIs, SNRIs, bupropion, mirtazapine and vortioxetine are the recommended first-line pharmacological options, while TCAs and MAOIs carry more risk and are used later. ^{[3] [1]}
• The most important decisions are how you start, review, warn about suicidality, avoid interactions and stop. ^[1]
• Serotonin syndrome is a rapid, concentration-dependent toxidrome of cognition, autonomic activity and neuromuscular excitation; stop the trigger first and treat hyperthermia and rigidity aggressively. ^[4]
• Lithium is the most effective long-term treatment for bipolar disorder and requires a fixed programme of blood monitoring. ^[2]

By the end of this page you should be able to:

1. Name the major antidepressant classes and mood stabilisers, their mechanisms, and representative members.
2. Explain why an SSRI or SNRI is usually first line and when a TCA, MAOI, mirtazapine, bupropion or vortioxetine suits the patient better.
3. Select a realistic adult starting and maintenance dose and describe titration.
4. Predict and explain the important adverse effects of each drug, including weight gain, sedation and sexual dysfunction.
5. Recognise serotonin syndrome, distinguish it from neuroleptic malignant syndrome, and outline its step-wise management.
6. Design a monitoring plan for SSRIs, lithium, valproate, lamotrigine and carbamazepine with correct intervals and actions.
7. Plan how to start, review and stop (with tapering) an antidepressant safely.
8. Summarise how NICE, CANMAT and Maudsley differ and when that matters.

Depression is common, disabling and treatable, while mood stabilisers convert a relapsing bipolar illness into a largely outpatient-managed one. This page covers both groups together because the same prescriber, patient, and laboratory infrastructure link them: antidepressants used alone in bipolar disorder can switch mood into mania, and lithium requires the same careful monitoring machinery as an antidepressant being tapered. The doses are typical adult oral doses and must be checked against your local formulary and product information.

Four questions organise the pharmacology:

1. Which monoamine signal does the drug change, by what mechanism, and for how long?
2. What clinical problem does that match (depression, anxious depression, neuropathic pain, bipolar depression, mania maintenance)?
3. What does it cost the patient (weight, sedation, sexual function, bleeding, QT risk, seizure risk, interaction load)?
4. What must be measured, and how often, to keep it safe?

A mood stabiliser here means a drug with evidence for reducing relapse in bipolar disorder. The classes and their common representatives are:

Lithium is the classic outlier: about 80 years of use have not produced one accepted cellular mechanism, yet it is the drug with the strongest evidence for preventing relapse and suicide in bipolar disorder. ^[2]

Monoamine synapses recycle transmitter by pumping it back into the presynaptic terminal. Tricyclics, SSRIs and SNRIs all block this pump, so more transmitter remains in the synaptic cleft. The classes differ in which pump they prefer: fluoxetine at the serotonin transporter, desipramine at the noradrenaline transporter, duloxetine at both. MAOIs work one step earlier, stopping the enzyme that degrades monoamines inside the terminal. The downstream result in both cases is increased postsynaptic serotonin (especially 5-HT1A and 5-HT2A) and noradrenaline signalling.

The synaptic change happens within hours, whereas the antidepressant effect takes two to four weeks. The accepted explanation is that the initial rise in synaptic serotonin first produces side effects such as activation, nausea and anxiety, while therapeutic benefit depends on slower adaptive changes, including desensitisation of somatodendritic 5-HT1A autoreceptors and enhanced neuroplasticity. This delay is why patients should not judge the drug too early and why safety planning matters in the first fortnight. ^{[1][3] [4]}

Mirtazapine is not a reuptake blocker. It antagonises presynaptic alpha-2 adrenergic autoreceptors, increasing noradrenaline release, and 5-HT2 and 5-HT3 receptors, directing serotonin through 5-HT1A receptors. It is therefore sedating and appetite-stimulating and much less likely to cause nausea or sexual dysfunction. ^[3]

Bupropion inhibits dopamine and noradrenaline reuptake and has no direct serotonergic action. That explains both its advantages (less sexual dysfunction, less weight gain) and its main caution (lower seizure threshold). ^[3]

Vortioxetine blocks serotonin reuptake and acts at several serotonin receptor subtypes (agonist at 5-HT1A, partial agonist at 5-HT1B, antagonist at 5-HT1D, 5-HT3 and 5-HT7). In pooled analyses it has the largest cognitive effects among antidepressants. ^[3]

Mood stabilisers have more modest mechanistic stories. Valproate facilitates GABA-ergic transmission and blocks voltage-sensitive sodium channels. Carbamazepine blocks voltage-gated sodium channels and induces hepatic enzymes, which lowers concentrations of many co-prescribed drugs. Lamotrigine inhibits voltage-sensitive sodium channels and modulates glutamate release. Their mood-specific mechanisms are less defined than their anticonvulsant ones. ^[2]

SSRIs are well absorbed and most are metabolised by cytochrome P450 enzymes in the liver. Half-lives are usually one to three days, except for fluoxetine and its active metabolite norfluoxetine, whose combined half-lives can stretch to several weeks. That is the reason fluoxetine is the easiest SSRI to stop and the hardest to wash out before an MAOI. ^[1][3]

TCAs are lipophilic, highly protein-bound, have long half-lives and are metabolised in the liver with wide inter-individual variation. After overdose they are particularly dangerous because their anticholinergic and cardiac sodium-channel effects dominate before clearance. ^[3]

Venlafaxine has a short half-life and an active metabolite, desvenlafaxine, so withdrawal symptoms are common. Duloxetine is metabolised mainly by CYP1A2 and CYP2D6. Bupropion inhibits CYP2D6 and is metabolised to hydroxybupropion. Mirtazapine is metabolised by CYP2D6, CYP1A2 and CYP3A4. Vortioxetine depends on CYP2D6, so inhibitors raise its level. ^[3]

For the mood stabilisers, lithium is not metabolised and is cleared almost entirely by the kidneys: any change in renal function, sodium intake, hydration or interacting drug changes the level. Valproate is hepatically metabolised and highly protein-bound. Lamotrigine is glucuronidated; valproate inhibits that process and can roughly double lamotrigine concentration, which is why lamotrigine must be titrated far more slowly in valproate users. Carbamazepine induces its own metabolism, so levels fall over the first weeks after starting. ^{[2][6] [3]}

Antidepressants are used far beyond major depression:

• Major depressive disorder, single or recurrent. ^[1][3]
• Anxiety disorders, panic, social anxiety, obsessive-compulsive disorder and post-traumatic stress disorder (mainly SSRIs and SNRIs). ^[3]
• Bipolar depression, only with a mood stabiliser or antipsychotic: fluoxetine with olanzapine, quetiapine, or lamotrigine. ^[2]
• Neuropathic and fibromyalgia pain: duloxetine and TCAs. ^[3]
• Chronic pain, insomnia and nocturnal enuresis: TCAs and mirtazapine in selected patients. ^[3]
• Migraine prophylaxis: amitriptyline. ^[3]

Mood stabilisers are used for:

• Acute mania or hypomania. ^[2]
• Bipolar depression. ^[2]
• Long-term prophylaxis, where lithium is the most effective. ^[2]
• Augmentation in treatment-resistant unipolar depression: lithium. ^[1]

Typical adult oral doses from the guideline tables. These are starting points that must be individualised, and the maximum for a given patient is the one in your formulary. ^[3]

Practical titration rules shared by major guidelines:

• Reassess tolerability, safety and early improvement no later than two weeks after starting. ^[3]
• If the drug is going to work, improvement is usually seen within four weeks. ^[1]
• Increase the dose for non-improvers at two to four weeks if the drug is tolerated, rather than switching immediately. ^[3]
• Continue treatment for at least six months after remission before considering withdrawal. ^[1]
• Lithium target: 0.6 to 0.8 mmol per litre if prescribing for the first time; 0.8 to 1.0 mmol per litre for at least six months if the patient has previously relapsed on lithium or has subthreshold symptoms with functional impairment. When lithium is used to augment an antidepressant, levels are usually at or above 0.4 mmol per litre and never above 1.0 mmol per litre. ^[1][2]

Renal and hepatic adjustment. Reduce the dose or extend the dosing interval in renal impairment, especially for lithium, and use great caution with CYP-dependent drugs in hepatic impairment. Older adults need lower doses, slower titration and closer monitoring for hyponatraemia and falls. ^[1][3]

Each drug class has a predictable footprint, most of it explainable from its mechanism:

• SSRIs: early nausea and diarrhoea, activation or akathisia, headache, sweating, insomnia or somnolence, sexual dysfunction that may persist after stopping, and hyponatraemia in older adults. Bleeding risk is increased, especially with NSAIDs, and falls risk peaks in the first six weeks. ^[1][3]
• SNRIs: a dose-related blood pressure rise and activation, with less sexual dysfunction than paroxetine but more than bupropion. ^[3]
• TCAs: antimuscarinic effects (dry mouth, constipation, urinary retention, confusion), orthostatic hypotension, weight gain, QT prolongation and high lethality in overdose. ^[1][3]
• Mirtazapine: sedation and appetite or weight gain, but little sexual dysfunction or nausea. ^[3]
• Bupropion: activating, usually taken in the morning; contraindicated in epilepsy and eating disorders because of seizure risk. ^[3]
• Vortioxetine: dose-dependent nausea; otherwise generally well tolerated. ^[3]
• Agomelatine: elevation of liver enzymes in a minority; regular liver function testing is required. ^[3]
• MAOIs: dietary tyramine precautions, severe interactions and hypertensive crises; moclobemide and the selegiline patch are gentler. ^[3]
• Lithium: tremor, polyuria and polydipsia, hypothyroidism, hyperparathyroidism with raised calcium, weight gain and long-term renal effects. ^[2]
• Valproate: weight gain, tremor, hair thinning, hepatotoxicity, pancreatitis and teratogenicity. ^[2]
• Carbamazepine: rash, diplopia and ataxia, hyponatraemia, hepatic enzyme induction, blood dyscrasias and severe skin reactions, including Stevens-Johnson syndrome in susceptible ancestry. ^[2][6]
• Lamotrigine: generally well tolerated, but severe skin reactions including Stevens-Johnson syndrome, especially with rapid titration or valproate co-treatment. ^[2]

Why the effects occur. Anticholinergic burden explains the TCA dry mouth, constipation and cognitive slowing; alpha-1 blockade explains hypotension; H1 blockade explains sedation and weight gain. Gut serotonergic activation explains early nausea and diarrhoea. Noradrenaline reuptake blockade explains the blood pressure rise with venlafaxine. Sodium-channel effects explain much of the anticonvulsant mood stabiliser profile. ^[3]

Safety bottom lines:

• Baseline and follow-up pulse and blood pressure are needed with venlafaxine and antipsychotic augmentation. ^[1][2]
• Liver function testing is mandatory for agomelatine; routine liver testing is not needed for most antidepressants. ^[3]
• Hyponatraemia, falls and fractures concentrate in older adults and in the first six weeks. ^[1][3]
• Torsade de pointes is very rare at therapeutic doses, but ECG monitoring is prudent with cardiac risk or QT-prolonging co-medication. ^[3]
• SSRIs modestly increase gastrointestinal bleeding, and NSAIDs roughly double that risk; acid suppression reduces it. ^[3]

• Do not routinely prescribe TCAs to people at significant risk of suicide, because they are the most dangerous antidepressants in overdose; lofepramine is the exception. ^[1]
• SSRIs must not be used if the patient enters a manic phase. ^[1]
• Bupropion is contraindicated in epilepsy and eating disorders, and is avoided with MAOIs or conditions lowering seizure threshold. ^[3]
• MAOIs need dietary tyramine restriction and careful washout with serotonergic drugs. ^[3]
• Agomelatine is contraindicated in active liver disease or with hepatotoxic drugs, and requires liver monitoring. ^[3]
• Lithium should not be started without the capacity for serum level monitoring and is avoided in severe renal impairment. ^[2]
• Valproate must not be started in men or women under 55 without the MHRA specialist conditions, and must not be used in women able to have children unless the NICE box 1 conditions are met. ^[2]
• Carbamazepine requires HLA-B*1502 screening in patients of Han Chinese or Thai ancestry. ^[6]

Interaction load is a practical reason drugs are chosen or rejected.

• CYP interactions: fluoxetine and paroxetine are strong CYP2D6 inhibitors, fluvoxamine inhibits CYP1A2, 2C19 and 3A4, and bupropion, duloxetine and sertraline are moderate CYP2D6 inhibitors; agomelatine, duloxetine and vilazodone follow predictable CYP patterns. ^[3]
• MAO interactions: serotonin syndrome or hypertensive crisis can occur when serotonergic or sympathomimetic drugs are combined with MAOIs. ^[3]
• Lithium interactions: ACE inhibitors, angiotensin receptor blockers, thiazide and loop diuretics and NSAIDs raise lithium levels or damage renal function; lithium with anticonvulsants increases neurotoxicity. ^[1][2]
• Valproate with other anticonvulsants: valproate raises lamotrigine levels, so lamotrigine must be titrated much more slowly. ^[2]
• Carbamazepine is an inducer: it lowers concentrations of many drugs, induces its own metabolism and requires brand prescribing. ^[2][6]
• Alcohol, nicotine and caffeine matter clinically; St John's wort is an inducer and must be avoided with serotonergic drugs. ^[1]

Serotonin syndrome, more accurately called serotonin toxicity, is a rapid, potentially life-threatening toxidrome from excessive synaptic serotonin. It is concentration-driven rather than allergic. ^[4]

Mechanism. Serotonin acts on at least seven receptor families. 5-HT1A stimulation probably drives milder neuromuscular and anxious features; 5-HT2A stimulation, needing much higher serotonin concentrations, drives hyperthermia and rigidity. Severe toxicity usually requires a massive rise, most often an MAOI combined with another serotonergic agent. ^[4]

When it happens. Three scenarios: shortly after starting or increasing a serotonergic drug, after overdose, or after a drug-drug interaction such as SSRI plus MAOI. Symptoms begin within an hour in about 30% of patients and within six hours in 60%. ^[4]

Clinical features. Mental status (agitation, confusion), autonomic signs (tachycardia, mydriasis, sweating, hyperthermia above 40 degrees in severe disease), and neuromuscular signs (tremor, hyperreflexia, clonus, myoclonus, rigidity). Clonus is the most specific sign; life-threatening disease shows truncal rigidity, opisthotonus and respiratory compromise. ^[4]

Diagnosis. It is a clinical diagnosis. The Hunter Serotonin Toxicity Criteria are the most commonly used but were derived and validated in overdose rather than stable patients, so they can over-diagnose toxicity in someone merely unwell on a serotonergic drug. A definite serotonergic exposure or interaction, with exclusion of other causes, is needed. ^[4]

Management. Stop the serotonergic drug and provide escalating supportive care:

Cautions: serotonin antagonists are widely used but lack controlled evidence of benefit on mortality or complications, and cyproheptadine is only oral. Empirical use may relieve symptoms in mild-to-moderate disease but must not delay resuscitation in severe disease. Severe toxicity usually settles within 24 hours of stopping the trigger and starting supportive care; long half-life drugs last longer. ^[4]

Differentiation from neuroleptic malignant syndrome. NMS follows dopamine antagonists, not serotonergic drugs; it shows lead-pipe rigidity and bradykinesia rather than clonus, often with a markedly elevated creatine kinase. The drug history and the presence of clonus are the practical discriminators. ^[4]

Stopping an antidepressant should be planned. About 20% of patients develop an antidepressant discontinuation syndrome after abrupt cessation or a marked dose reduction of a drug taken for one month. The syndrome is usually mild, can occur with any antidepressant, starts two to four days after stopping and lasts one to two weeks, occasionally up to a year. ^[5]

The FINISH mnemonic: flu-like symptoms, insomnia with vivid dreams, nausea, imbalance (dizziness, vertigo), sensory disturbances (electric shock or burning sensations) and hyperarousal (anxiety, irritability, agitation, even mania). ^[5]

Recognition matters. The syndrome is commonly misdiagnosed as relapse, infection or something else. Relapse of depression takes more than a few days to develop and does not usually resolve within a day or two of restarting the drug. ^[5]

Drug-specific risk varies. Paroxetine has the highest incidence, fluoxetine the lowest because of its long half-life, and venlafaxine is more likely to produce a severe syndrome because of its short half-life. ^[5]

NICE practical rules: explain before starting, taper in step-wise reductions, often halving the dose each step, then considering 25% decrements at lower doses, and use liquid preparations when tablets cannot make a very small dose. Allow one to two weeks before each next reduction. Fluoxetine can be tapered with alternate-day dosing at 20 mg daily or a gradual schedule at higher doses. Antidepressants with very short half-lives need slower tapers. ^[1]

Prevention and counselling: tapering may not be needed after less than four weeks of treatment or with fluoxetine; faster tapering may be possible at low doses; switching to fluoxetine during withdrawal of another antidepressant can help; and if symptoms are severe, reintroduce the previous dose and begin a slower taper. Patients should be reassured that symptoms are reversible, not life-threatening and usually self-limiting. Six to eight weeks of tapering reduces risk. ^[1][5]

Routine follow-up means reviewing people with depression between two and four weeks after starting, and monitoring side effects, adherence, suicidal ideation and outcomes. In people at risk of suicide, review them one week after starting or increasing the dose and no later than four weeks. ^[1]

Lithium augmentation of antidepressants requires baseline weight, renal and thyroid function and calcium, then monitoring at least every six months. Lithium levels are monitored 12 hours post-dose, one week after starting or dose change, then weekly until stable, three-monthly in the first year and then six-monthly, or three-monthly for older adults, people on interacting drugs, impaired renal or thyroid function, high calcium, poor symptom control, poor adherence, or a last level of 0.8 mmol per litre or higher. Warn patients to seek attention for diarrhoea, vomiting or dehydration and to watch for toxicity signs (diarrhoea, vomiting, coarse tremor, ataxia, confusion, convulsions), which can occur at therapeutic levels. ^[1]

Lithium is first-line long-term treatment for bipolar disorder and also augments antidepressants; its narrow index requires a fixed monitoring programme. ^[1][2]

• Target range: 0.6 to 0.8 mmol per litre when prescribing for the first time; 0.8 to 1.0 mmol per litre for at least six months if the patient has relapsed on lithium or has subthreshold symptoms with functional impairment. ^[2]
• Augmentation of antidepressants: usually at or above 0.4 mmol per litre, never above 1.0 mmol per litre; 0.4 to 0.6 mmol per litre in adults aged 65 or over. ^[1]
• Levels: one week after starting or every dose change, then weekly until stable; every three months in the first year, then every six months, or every three months in at-risk groups; samples taken 12 hours post dose. ^[1][2]
• Physical monitoring: weight or BMI and urea and electrolytes including calcium, estimated glomerular filtration rate and thyroid function every six months or more often if abnormal. ^[1][2]
• ECG if cardiac risk or disease; counselling on consistent sodium and fluid intake and dehydration risk. ^[1][2]
• Neurotoxicity (paraesthesia, ataxia, tremor, cognitive impairment) can occur even at therapeutic levels. ^[2]
• Stopping: taper over at least four weeks, preferably up to three months. ^[1][2]

NICE recommends valproate for mania or hypomania, for bipolar depression at higher tolerated doses, and long-term in combination with lithium if lithium is insufficient. Semi-sodium valproate gained a UK marketing authorisation for some of these uses in 2025. ^[2]

• Do not start valproate for the first time in men or women under 55 unless two specialists independently agree and document that no other effective, tolerated treatment exists or that the reproductive risks do not apply. ^[2]
• In women and girls able to have children, it may only be used if other options are ineffective or not tolerated, risks and benefits (including fetal risks) are fully discussed, and the Pregnancy Prevention Programme is used where appropriate. ^[2]
• Men on valproate need effective contraception throughout treatment and for three months after stopping and should be counselled about fertility. ^[2]
• Do not routinely measure plasma valproate levels unless there is evidence of ineffectiveness, poor adherence or toxicity. ^[2]
• Measure weight or BMI and repeat liver function tests and full blood count after six months of treatment, and repeat annually. ^[2]
• Monitor sedation, tremor and gait carefully in older people. ^[2]
• Be aware of interactions with carbamazepine, lamotrigine, olanzapine and smoking. ^[2]
• Stop immediately if aggravated liver dysfunction or acute liver disease; raised hepatic enzymes with reduced albumin or impaired clotting suggest severe liver disease. ^[2]
• If stopping, reduce gradually over at least four weeks, preferably up to three months. ^[2]

Lamotrigine is recommended for bipolar depression, on its own or added to lithium or valproate, and for prevention in predominantly depressive illness. It must not be used to treat mania. ^[2]

• Plasma levels are not routinely needed unless there is evidence of ineffectiveness, poor adherence or toxicity. ^[2]
• Slow titration is essential; titrate even more slowly with valproate because valproate inhibits glucuronidation. ^[2]
• Treat any rash seriously in the first weeks to months because of the risk of Stevens-Johnson syndrome. ^[2]

Carbamazepine is licensed for mania prophylaxis unresponsive to lithium but is not a NICE first-line option and has less robust evidence. ^[2] Its monitoring schedule follows the specialist pharmacy service. ^[6]

• Baseline: weight or BMI, full blood count, liver function tests, urea and electrolytes, serum sodium, and HLA-B*1502 screening for Han Chinese and Thai patients. ^[6]
• After starting or changing dose: serum sodium at two weeks and then monthly for three months if the patient has renal impairment or takes sodium-lowering medicines; ECG if cardiovascular risk factors. ^[6]
• Routine plasma carbamazepine levels are not recommended, but when checked the optimum range is 4 to 12 mg per litre (20 to 50 micromol per litre). ^[6]
• Ongoing: periodic urea and electrolytes, liver function tests (especially in older adults or liver disease) and vitamin D; discontinue for severe or progressive leucopenia with fever or sore throat or for significant bone marrow suppression; withdraw immediately for aggravated liver dysfunction or acute liver disease. ^[6]
• Hyponatraemia below 120 mmol per litre with symptoms means review treatment; asymptomatic mild hyponatraemia above 120 mmol per litre can be observed. ^[6]
• Warn patients and carers to report fever, sore throat, rash, mouth ulcers, bruising or bleeding and any suicidal thoughts urgently. ^[6]
• Carbamazepine is an MHRA category 1 medicine: maintain a specific manufacturer's preparation in epilepsy and prescribe by brand. ^[6]

NICE is a process and consensus guideline that puts patient choice, non-pharmacological treatment, review intervals and withdrawal management first and restricts antidepressants as first-line for less severe depression. ^[1] CANMAT (2016) is a prescriber's manual in question-and-answer form with explicit lines of treatment, typical doses and side-effect tables. ^[3] The Maudsley Prescribing Guidelines (14th edition) is the bedside and shared-care handbook, foregrounding the lowest possible dose, interaction checks, physical comorbidity and the need for a clear monitoring record. ^[7]

Practical differences: CANMAT calls venlafaxine first line where many UK prescribers use an SSRI first; NICE groups vortioxetine as first line by class rather than giving it a distinct role; national valproate rules have become far stricter since these texts were written, so valproate is now effectively third line in many jurisdictions for women who could become pregnant. ^[1][2][3]

Antenatal and postnatal management outside these guidelines belongs to the perinatal mental health team. ^[1][2]

• SSRIs (especially sertraline) are commonly used in pregnancy and breastfeeding with informed discussion, because untreated depression carries its own risks. Valproate and carbamazepine are teratogenic; valproate is under the MHRA Pregnancy Prevention Programme. ^[2]
• Lithium can be used in pregnancy in selected cases but needs close specialist monitoring and pre-conception planning. ^[1]
• There is a small increased risk of postpartum haemorrhage with SSRI or SNRI use in the month before delivery. ^[3]
• Breastfeeding choices should follow product guidance; sertraline, paroxetine and fluoxetine have the best documented paediatric experience. ^[3]

Stopping a drug that has worked is not always safer than continuing it; these decisions should be documented and shared with the patient. ^[1]

Older adults are the group in which these drugs do most harm. SSRIs cause hyponatraemia, falls and fractures, especially in the first six weeks. TCAs add anticholinergic cognitive burden and orthostatic hypotension. Lithium is cleared less efficiently and accumulates at ordinary doses, so monitoring should be more frequent and the target level lowered. Lamotrigine and valproate need lower starting doses and fuller baseline screening. ^[1][2][3]

• A structured clinical assessment, psychoeducation and an SSRI with few interactions are the realistic psychiatric building blocks, although much monitoring assumes laboratory access. ^[3]
• Lithium should be avoided or the patient transferred when reliable assays are unavailable, rather than guessing.
• Carbamazepine and valproate levels are usually available even where fuller panels are not; pair them with clinical toxicity checks. ^[6]
• Valproate should be avoided in pregnancy wherever possible. ^[2]

• Major depression of moderate or greater severity deserves pharmacological treatment; SSRIs and SNRIs are preferred first line because of tolerability. ^[1][3]
• TCAs and MAOIs are effective; reserve them for specific indications or after first-line failure because of overdose and interaction risk. ^[1][3]
• Bupropion, mirtazapine and vortioxetine are first-line choices selected for side-effect profile, not superior efficacy. ^[3]
• Therapeutic effect is delayed by two to four weeks; patients must be warned and safety-planned in that window. ^[1][3]
• Review treatment at two to four weeks and withdraw only when the patient is stable and agrees. ^[1]
• Avoid TCAs in suicidal patients and control quantity dispensed. ^[1]
• Serotonin syndrome develops within hours, is driven by combinations and MAOIs and is managed by stopping the trigger and treating hyperthermia and rigidity. ^[4]
• Withdrawal symptoms start within days and last up to two weeks; taper gradually, faster only at low doses, and reassure the patient. ^[1][5]
• Paroxetine and venlafaxine have the highest discontinuation risk; fluoxetine the lowest. ^[5]
• Lithium is the most effective long-term bipolar treatment and requires pre-treatment and six-monthly renal, thyroid and calcium monitoring plus serum levels on a strict schedule. ^[1][2]
• Valproate is restricted in under-55s and in women who could become pregnant, and needs liver and blood checks. ^[2]
• Carbamazepine needs baseline bloods, sodium and HLA-B*1502 screening, brand prescribing and has a therapeutic range of 4 to 12 mg per litre when levels are checked. ^[6]
• Lamotrigine is the bipolar depression drug: slow titration, no routine levels, high vigilance for rash. ^[2]
• SSRIs raise bleeding risk with NSAIDs, cause hyponatraemia in older adults and need QT caution with citalopram and escitalopram. ^[1][3]
• Antidepressants for bipolar depression are always given with a mood stabiliser or antipsychotic. ^[2]

Plain text: bipolar disorder and its management; major depressive disorder; anxiety disorders; medicines associated with dependence and withdrawal; lithium in bipolar disorder; pregnancy and mental health; postpartum mental health; older adult prescribing in psychiatry.