Psychotropic Medication

Introduction

Psychotropic medications are among the most widely prescribed drugs in the UK, and are prescribed far more often outside psychiatry than within it. Understanding how they work, how to choose between them, and what to monitor is core general medical knowledge rather than specialist territory.¹

This article gives an overview across the main classes and, importantly, the drug-induced emergencies that follow when they interact badly or are monitored poorly. Individual conditions are covered in their own articles; the aim here is to draw the pharmacology together in one place.

Two principles run through everything that follows. First, efficacy across most agents within a class is broadly comparable, so the choice is usually driven by side-effect profile, comorbidity and patient preference rather than by potency. Second, monitoring is part of the prescription - the physical health consequences of psychotropics, particularly antipsychotics, contribute substantially to the reduced life expectancy seen in people with severe mental illness, and neglecting it causes real harm.

Antidepressants

All current antidepressants work by increasing the availability of monoamine neurotransmitters - serotonin, noradrenaline, or both - at the synapse. The monoamine hypothesis is an incomplete explanation, since receptor effects are immediate while clinical response takes weeks, implicating downstream neuroplastic changes.

Practical prescribing

• Onset - some improvement in sleep and appetite may occur within 1-2 weeks, but full antidepressant effect typically takes 4-6 weeks. Judge response at an adequate dose and duration before switching.
• Early worsening - anxiety and agitation may increase in the first 1-2 weeks. Warn patients explicitly, as this is a common reason for stopping treatment prematurely.
• Suicidality - a small increased risk of suicidal thoughts in those under 25; review within 1 week of starting in this group, and within 2 weeks otherwise
• Continuation - continue for at least 6 months after remission of a first episode, and 2 years or longer after recurrent episodes
• Hyponatraemia - a well-recognised SSRI effect through SIADH, particularly in older adults; check sodium if a patient becomes confused, drowsy or falls
• Bleeding risk - SSRIs impair platelet aggregation; consider gastroprotection when co-prescribed with NSAIDs or anticoagulants

Antipsychotics

All effective antipsychotics block dopamine D2 receptors. Therapeutic benefit comes from blockade in the mesolimbic pathway, but the same blockade elsewhere produces the characteristic side effects - nigrostriatal blockade causing extrapyramidal effects and tuberoinfundibular blockade causing hyperprolactinaemia.

Extrapyramidal side effects

Other important side effects

• Metabolic - weight gain, dyslipidaemia and type 2 diabetes, most marked with olanzapine and clozapine
• Hyperprolactinaemia - galactorrhoea, amenorrhoea, gynaecomastia, sexual dysfunction and reduced bone density
• QTc prolongation - notably haloperidol; check an ECG before and after starting
• Anticholinergic effects - dry mouth, constipation, urinary retention, blurred vision, cognitive impairment
• Postural hypotension - through alpha-1 blockade, with falls risk in older adults
• Reduced seizure threshold
• Increased risk of stroke and death in older people with dementia - antipsychotics should be avoided for behavioural symptoms of dementia except where there is severe distress or risk, and then at the lowest dose for the shortest time

Clozapine

Clozapine is the only antipsychotic with demonstrably superior efficacy in treatment-resistant schizophrenia - defined as failure to respond to two adequate trials of different antipsychotics, at least one being second-generation. It also reduces suicidality.

Mood stabilisers

Lithium in detail

• Therapeutic range typically 0.6-0.8 mmol/L, measured 12 hours post-dose; weekly after initiation or dose change until stable, then every 3 months
• U&Es and TFTs every 6 months - lithium causes hypothyroidism, hyperparathyroidism and nephrogenic diabetes insipidus, and can cause chronic renal impairment with long-term use
• Interactions that raise levels - NSAIDs, ACE inhibitors and ARBs, thiazide diuretics, and dehydration from any cause including diarrhoea, vomiting or hot weather
• Toxicity - coarse tremor (contrast with the fine tremor of therapeutic use), ataxia, slurred speech, vomiting, diarrhoea, confusion, seizures and, at severe levels, coma and renal failure
• Management of toxicity - stop lithium, give IV fluids, check levels and renal function, and consider haemodialysis in severe toxicity
• Never stop lithium abruptly in a stable patient - abrupt discontinuation carries a high risk of rebound mania⁴

Anxiolytics and hypnotics

• Benzodiazepines (diazepam, lorazepam, temazepam) - GABA-A positive allosteric modulators. Rapidly effective for acute anxiety, agitation, alcohol withdrawal and status epilepticus, but cause tolerance and dependence. Use for no more than 2-4 weeks, and never stop abruptly - convert to long-acting diazepam and taper slowly over months if the patient is dependent.
• Z-drugs (zopiclone, zolpidem) - act at the same receptor complex; marketed as safer for insomnia but carry a comparable dependence risk. Short-term use only, alongside sleep hygiene advice.
• Promethazine - a sedating antihistamine, non-dependence-forming, useful as an alternative for short-term insomnia
• Pregabalin - licensed for generalised anxiety disorder, but now a controlled drug with recognised misuse potential and a significant risk of respiratory depression when combined with opioids
• Beta-blockers (propranolol) - reduce the physical symptoms of anxiety such as tremor and palpitations, but do not treat the underlying anxiety
• Melatonin - for insomnia, particularly in older adults, children with neurodevelopmental conditions, and circadian rhythm disorders

Psychotropic emergencies

Three syndromes must be reliably distinguished, since they present similarly but have entirely different causes and treatments. This is one of the most heavily examined areas in psychiatric pharmacology.²

Physical health monitoring

People with severe mental illness die on average 15-20 years earlier than the general population, predominantly from cardiovascular disease rather than suicide. Antipsychotics contribute directly through weight gain, dyslipidaemia and diabetes, and monitoring is therefore a core clinical duty rather than an administrative task.³

Alongside monitoring, actively address modifiable risk: smoking cessation (rates are markedly higher in this population, and cessation also raises clozapine levels so needs dose review), diet and exercise support, and treatment of hypertension, diabetes and dyslipidaemia to the same standard as anyone else - which is frequently not what happens in practice.

Red flags

Summary

Choosing a psychotropic is usually a matter of matching side-effect profile to the individual rather than of selecting the most potent agent, since efficacy within most classes is broadly comparable. Explaining the expected timeline honestly - weeks rather than days, with possible early worsening - is one of the most effective things a prescriber can do to support adherence.

The recurring themes are that monitoring is inseparable from prescribing, that abrupt discontinuation causes harm across almost every class, and that a small number of drug-induced emergencies account for most of the serious morbidity. Knowing lithium's monitoring requirements, clozapine's mandatory blood counts, valproate's absolute contraindication in women of childbearing potential, and how to tell serotonin syndrome from neuroleptic malignant syndrome will cover the majority of what is examined and, more importantly, most of what causes avoidable harm in practice.