CASC Knowledge Essentials15 · Psychotropic medicines and ECT
15 · Psychotropic medicines and ECT
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Written by Resident Doctor Committee · Published
15.1 Antipsychotic effects make sense through receptors
Most antipsychotics reduce D2 signalling; aripiprazole is a partial agonist. The pathway matters: dopamine blockade can reduce psychosis, cause movement problems and raise prolactin in the same patient.
Action | Consequence |
|---|---|
Reduced dopamine signalling in salience pathways | Fewer hallucinations and delusions |
Nigrostriatal D2 blockade | Extrapyramidal effects |
Tuberoinfundibular D2 blockade | Removes dopamine's inhibition of prolactin release |
H1 antagonism | Sedation and increased appetite |
Muscarinic antagonism | Dry mouth, constipation, blurred vision, urinary retention, cognitive impairment |
Alpha-1 blockade | Postural hypotension and falls |
Compare individual drugs. Clozapine/olanzapine carry substantial metabolic risk. Risperidone/paliperidone/amisulpride commonly raise prolactin. Aripiprazole usually has lower prolactin and metabolic burdens, but can cause marked akathisia. “Second generation” does not mean free of movement effects.
15.2 Raised prolactin and metabolic harm
Raised prolactin suppresses the gonadal axis. Look for low libido, erectile/orgasmic difficulty, menstrual disturbance, infertility and galactorrhoea. Prolonged hypogonadism harms bone health. Other causes include pregnancy, hypothyroidism, renal impairment and pituitary disease; headache or visual-field loss raises concern about the last.
Options include dose reduction, a prolactin-sparing switch or specialist adjunctive aripiprazole. Dopamine agonists may worsen psychosis. Use the laboratory range and clinical picture, not a universal MRI threshold. When ovulation returns, fertility can return.
Metabolic harm can occur without obvious weight gain. Insulin resistance, dyslipidaemia and hypertension all matter. Thirst/polyuria suggest hyperglycaemia; vomiting or altered consciousness may indicate ketoacidosis. Treat physical risk while weighing the psychiatric benefit, especially when clozapine is the first effective treatment.
Baseline antipsychotic checks: weight, waist, pulse/BP, glucose or HbA1c, lipids, prolactin and movement assessment. ECG for relevant cardiac risk, inpatient admission or a product requirement.
Measurement | NICE follow-up |
|---|---|
Weight | Weekly for six weeks; then 12 weeks, one year, annually |
Pulse/BP | 12 weeks, one year, annually |
Glucose/HbA1c and lipids | 12 weeks, one year, annually |
Waist | Annually |
Symptoms/movement effects | Regularly, especially during titration |
Symptoms or abnormal results need earlier checks.
15.3 Clozapine and treatment resistance
Two adequate antipsychotic trials have failed, including a non-clozapine second-generation drug: consider clozapine. First establish that the trials really were adequate: adherence and exposure matter. Other specialist uses include otherwise unmanageable neurological adverse effects and refractory Parkinson's psychosis.
Common effects | Serious problems to retain |
|---|---|
Sedation, hypersalivation, constipation | Gastrointestinal hypomotility, ileus/obstruction |
Weight gain, tachycardia, postural hypotension | Myocarditis, later cardiomyopathy |
Neutropenia/agranulocytosis and seizures |
Blood count versus plasma level
FBC detects blood-cell harm; plasma concentration measures drug exposure. A clozapine level can help with adherence, interactions and toxicity. It cannot replace the FBC.
UK Clozaril blood monitoring is at least weekly for 18 weeks → fortnightly to one year → four-weekly if stable, continuing for at least four weeks after stopping. Brand-linked services set eligibility, thresholds and interruption rules. Infection symptoms need urgent assessment/FBC even if the last result was normal.
More than 48 hours off clozapine: reassess and re-titrate from a low dose. Restarting the former full dose can cause cardiovascular collapse.
Same dose, higher concentration
Tobacco smoke induces CYP1A2; nicotine does not. Stopping cigarettes, including switching to vaping or nicotine replacement, can raise clozapine levels. Infection (particularly pneumonia) can also increase exposure. Olanzapine is affected by smoking changes too.
Increasing sedation, confusion, tachycardia, hypotension, seizures or gut problems may mean toxicity. Review clinically and check concentrations; there is no universal dose reduction for every patient.
Constipation: actively look for it
Clozapine slows the whole gut. Small stools or overflow diarrhoea do not exclude impaction. Pain, distension, vomiting, absent bowel sounds or systemic illness need urgent medical assessment.
Monitor bowel function and treat constipation. Stimulant/osmotic laxatives are commonly used after obstruction is excluded; bulk-forming laxatives are unsuitable for established hypomotility.
Myocarditis: tachycardia plus systemic features
Persistent resting tachycardia with fever, chest pain, breathlessness, unusual fatigue or cardiovascular deterioration is concerning, especially early in treatment. Troponin = myocardial injury; CRP = inflammation. A normal ECG does not exclude myocarditis.
Suspected myocarditis means withholding clozapine and urgent specialist assessment. Many initiation protocols include baseline/serial early CRP and troponin; use the local schedule.
15.4 Long-acting injections
A depot changes delivery, not the drug's systemic adverse effects. It makes missed treatment visible, but adverse effects may take longer to wear off. Injection-site pain/nodules are additional problems. Establish tolerability first; loading, oral overlap, injection site and missed-dose rules are product-specific.
Named preparation | Specific fact |
|---|---|
Risperdal Consta | Every two weeks; antipsychotic cover for the first three weeks because release is delayed |
Olanzapine pamoate: Zypadhera | Post-injection delirium/sedation risk; observe in a healthcare facility for at least three hours after every injection; no driving that day |
Do not apply Consta's rule to every risperidone formulation.
A depot does not itself imply treatment resistance. A CTO does not automatically authorise a forced injection at home.
15.5 Antidepressant adverse effects
Drug/group | Main recall points |
|---|---|
SSRIs | GI upset, sleep change, activation, sexual dysfunction; bleeding and hyponatraemia |
SNRIs, especially venlafaxine | Similar effects; pulse/BP may rise; prominent withdrawal |
Mirtazapine | Sedation, appetite/weight gain; often fewer sexual effects |
Tricyclics | Anticholinergic effects, sedation, postural hypotension, cardiac conduction toxicity; dangerous in overdose |
MAOIs | Food/drug interactions, including dangerous serotonergic combinations |
SSRIs and bleeding: platelets depend on serotonin uptake. NSAIDs, antiplatelets and anticoagulants add risk; assess the combination rather than declaring all SSRI use contraindicated. New confusion or falls after starting treatment may be hyponatraemia, particularly with older age or diuretics.
Sexual dysfunction: separate desire, arousal and orgasm
Depression can affect all three. An SSRI can leave mood better but cause delayed orgasm/anorgasmia. Consider diabetes, endocrine disease, other drugs and relationship factors; spontaneous erections do not fully exclude a physical cause.
Options include appropriate dose adjustment, switching or treating a specific problem. Mirtazapine may exchange sexual effects for weight gain. Sildenafil targets erectile dysfunction, not all low desire/orgasmic problems, and is contraindicated with nitrates. Unsupervised drug holidays risk withdrawal and loss of benefit.
Withdrawal is not the same as relapse
Dizziness, electric shocks, nausea, sweating, insomnia and anxiety after missed doses/reduction suggest withdrawal. It often starts sooner than relapse, but can be delayed or prolonged. Taper to the person's response. Antidepressants do not usually produce addictive craving/intoxication, yet physiological withdrawal is real.
QT-related maximum doses
Drug | Adult maximum/day | Over 65 or hepatic impairment |
|---|---|---|
Citalopram | 40 mg | 20 mg |
Escitalopram | 20 mg | 10 mg |
Congenital long QT, interacting drugs, bradycardia and electrolyte depletion still matter below the maximum.
15.6 Lithium
Uses include bipolar maintenance, mania and antidepressant augmentation. Renal elimination + narrow therapeutic index explain the monitoring: dehydration, kidney injury or an interacting drug can turn a previously safe dose toxic.
Monitoring and levels
When | What to check |
|---|---|
Baseline | Renal/thyroid function, electrolytes, calcium, weight, FBC; ECG for cardiac risk; pregnancy assessment where relevant |
Starting/changing dose | Level after about one week, then weekly until stable |
Routine sampling | 12 hours after the last dose |
Stable treatment | Levels three-monthly in year one, then every three to six months; more often in higher-risk patients |
Organ monitoring | Renal function, thyroid function and calcium generally six-monthly |
Bipolar maintenance: initially 0.6–0.8 mmol/L; selected patients need 0.8–1.0. Depression augmentation: often lower, usually at least 0.4, with lower targets considered in older adults. Match the target to indication, response and tolerability. Planned withdrawal is gradual: at least four weeks, preferably longer.
Ordinary adverse effects versus toxicity
Fine tremor, nausea, thirst and polyuria can occur at therapeutic levels. Longer-term concerns are hypothyroidism, hyperparathyroidism/hypercalcaemia, impaired urinary concentration and chronic renal impairment. Hypothyroidism can often be treated while lithium continues.
Nephrogenic diabetes insipidus: the kidney resists ADH, producing dilute urine and thirst. It is not SIADH. Levels may rise with NSAIDs, ACE inhibitors, ARBs and some diuretics, or with vomiting, diarrhoea, fever, dehydration and sodium-intake changes. Prescribe by brand/formulation.
Coarse tremor + ataxia, dysarthria, confusion, drowsiness or GI symptoms = suspect toxicity. It often occurs around/above 1.5 mmol/L, but can occur within the apparent usual range. Withhold lithium, obtain urgent lithium/renal/electrolyte tests and arrange urgent medical assessment. Do not wait for a 12-hour sample.
Pregnancy and breastfeeding need an individual specialist plan.
15.7 Other mood stabilisers
Drug | Knowledge to retain |
|---|---|
Valproate | Weight gain, tremor, GI effects, thrombocytopenia; serious liver injury/pancreatitis. Monitor weight, LFTs and FBC. Reproductive restrictions affect women and men differently. |
Lamotrigine | Bipolar depression/depressive relapse prevention, not acute mania. Slow titration reduces serious rash risk, including Stevens–Johnson syndrome. Valproate raises exposure; oestrogen-containing contraception lowers it |
Carbamazepine | Enzyme induction reduces hormonal contraceptive and other drug effects. Hyponatraemia, dizziness, ataxia, blood dyscrasias and serious rash |
A rash during lamotrigine titration needs prompt assessment, especially with mucosal lesions, fever or systemic illness. Starting/stopping interacting medication can require dose review.
15.8 NMS and serotonin toxicity
Both are medical emergencies. The exposure history and neuromuscular signs are the most useful separators.
Feature | NMS | Serotonin toxicity |
|---|---|---|
Exposure | Dopamine antagonist; sometimes dopaminergic-drug withdrawal | Serotonergic combination, overdose or drug change |
Tempo | Usually days | Usually hours |
Motor clue | Marked generalised rigidity | Clonus and hyperreflexia, often tremor |
Other features | Fever, confusion, autonomic instability; often raised CK | Agitation, sweating, diarrhoea, fever, autonomic instability |
Complications | Rhabdomyolysis, renal/cardiorespiratory failure | Severe hyperthermia, seizures, organ failure |
Stop culprit medicines and obtain urgent medical care/supportive monitoring. CK alone does not diagnose NMS; fever/rigidity may be less striking early. Specialist treatment may include benzodiazepines, dopaminergic drugs, dantrolene or ECT. BAP advises at least two weeks after NMS has resolved before antipsychotic reintroduction, with careful choice and slow titration.
Serotonergic combinations include an SSRI/SNRI with an MAOI, tramadol or linezolid. Switching may need a washout; fluoxetine persists particularly long. Benzodiazepines/supportive care are central; severe cases need toxicology/intensive care, and specialists may consider cyproheptadine. Clonus is the useful clue, although extreme rigidity can obscure it.
15.9 ECT
ECT induces a controlled seizure under general anaesthesia and muscle relaxation. Main indications: severe depression needing rapid improvement, especially life-threatening poor intake/psychosis; treatment-resistant severe depression; catatonia; selected severe/prolonged mania. Review the course individually.
Adverse effect | Meaning |
|---|---|
Anterograde memory problems | Difficulty learning new information |
Retrograde memory problems | Gaps in recall of earlier events |
Acute effects | Headache, muscle aches, transient confusion |
Standard cognitive-test performance usually recovers, but some autobiographical gaps can persist. Right unilateral ECT generally has a lower cognitive burden than bilateral treatment; adequate dosing matters for efficacy. Assess anaesthetic/cardiovascular risk.
Successful ECT still needs relapse prevention. Capacity and consent may change during a course. Detention does not automatically authorise ECT.
15.10 Repetitive transcranial magnetic stimulation (rTMS)
A coil held on the scalp, usually over the left dorsolateral prefrontal cortex, gives brief magnetic pulses that induce electric currents in the cortex beneath. No seizure is intended.
The patient is awake, with no anaesthetic. Intensity is usually set from the motor threshold (the weakest pulse that twitches the thumb), found first. Standard high-frequency sessions take about 30 minutes; intermittent theta-burst takes about 3 minutes and is non-inferior. Sessions run on weekdays for 4 to 6 weeks. The clicks are loud: earplugs protect hearing. Most people resume normal activities, including driving, the same day; some services advise not driving on the first day.
NICE (2015 procedures guidance): no major safety concerns; short-term efficacy adequate but response variable. Usable with normal governance; tell patients the alternatives and that it may not help. NICE's depression guideline adds nothing further. Consider it for treatment-resistant depression, or when antidepressants are unsuitable or ECT is declined or contraindicated. ECT is the better choice for very severe, psychotic or life-threatening depression, catatonia, or when a rapid response is needed.
Aspect | rTMS | ECT |
|---|---|---|
Anaesthetic | None | General, with muscle relaxant |
Seizure | Not intended; rare | Deliberately induced |
Schedule | Every weekday | Usually twice weekly |
Effect | Beats sham (NNT about 5 to 6); response varies | Greater, most clearly in psychotic depression |
Memory | No lasting effect found, autobiographical memory included | Problems common; some gaps can persist |
Consent | Usual capacity and consent rules; not section 58A | Section 58A safeguards |
Common: scalp discomfort and headache, usually mild and easing over the course; scalp or facial twitching during pulses. Rare: seizure (under 1 in 1,000), mostly in the first few sessions; a switch into hypomania (under 1%, as with sham), mainly in bipolar depression; brief concentration problems.
Contraindicated: ferromagnetic or electronic implants in or near the head (cochlear implant, deep brain stimulator, metal fragments); dental fillings are fine. Cautions: epilepsy or other seizure risk, such as brain injury, alcohol or benzodiazepine withdrawal, sleep deprivation or threshold-lowering drugs (for example clozapine).
Relapse is common. Continue antidepressants or psychological therapy; top-up sessions are used, though maintenance evidence is limited. NHS access is limited: some trusts treat patients referred from secondary care; otherwise treatment is private.
CASC: "A coil on your head sends magnetic pulses to a brain area involved in mood. You stay awake: no anaesthetic, no fit. It runs every weekday for several weeks, and you can carry on afterwards. It has not been found to harm memory, but it helps some people, not all, and ECT works for more." Traps: calling it a milder ECT; promising it will work; missing a history of hypomania or a seizure risk.
15.11 Medicines for dementia
Donepezil, rivastigmine and galantamine: acetylcholinesterase inhibition increases acetylcholine. Memantine: NMDA antagonism modifies glutamatergic signalling. They may improve symptoms/function; they do not cure Alzheimer's disease.
Alzheimer's disease | NICE treatment |
|---|---|
Mild–moderate | Acetylcholinesterase inhibitor |
Moderate, inhibitor unsuitable/not tolerated | Memantine alone |
Severe | Memantine |
Already taking an inhibitor | Consider adding memantine in moderate disease; offer in severe disease |
Do not stop a useful inhibitor solely because dementia becomes severe.
Cholinesterase inhibitors: GI upset, appetite/weight loss, bradycardia, syncope; donepezil may cause vivid dreams. Memantine: dizziness, headache, constipation/confusion; consider renal dosing. Rivastigmine patch: remove the old one before applying the new one.
Check baseline pulse, weight, electrolytes and relevant renal/liver function; consider ECG for cardiac/QT risk. SPS advises pulse monthly after initiation/dose changes, then six-monthly when stable.