Psychopharmacology and Biological Therapies: Medicines, Monitoring and ECT

Psychopharmacology is the rational use of medicines to reduce distress, restore function, prevent relapse and treat dangerous psychiatric syndromes. Biological therapies include medication, electroconvulsive therapy (ECT) and, in specialist services, other neuromodulation treatments. Safe prescribing begins with a formulation and shared decision; it does not begin with a drug name.

Learning objectives

• Explain how to choose a psychotropic medicine from the target syndrome, diagnosis, urgency, comorbidity, patient preference and monitoring capacity.
• Compare antidepressants, antipsychotics, mood stabilisers, anxiolytics, hypnotics, stimulants and medicines used for substance-related disorders.
• State important mechanisms, indications, contraindications, interactions, common adverse effects, serious toxicity and monitoring requirements.
• Recognise serotonin syndrome, neuroleptic malignant syndrome, acute dystonia, akathisia, tardive dyskinesia, lithium toxicity, valproate toxicity and benzodiazepine withdrawal.
• Explain the preparation, consent, indications, contraindications, adverse effects and aftercare of ECT.
• Construct a monitoring and patient-education plan that continues after the prescription is written.

1. Before prescribing: a safe clinical framework

1. Define the target. Name the syndrome or symptom to treat: psychosis, mania, depression, anxiety, insomnia, agitation, catatonia, withdrawal or relapse prevention.
2. Exclude urgent mimics. Check delirium, intoxication/withdrawal, hypoglycaemia, infection, epilepsy, endocrine disease, head injury and medication toxicity.
3. Assess risk. Suicide, violence, vulnerability, self-neglect, pregnancy, overdose access, QT risk and ability to follow monitoring all influence the plan.
4. Choose the least burdensome effective option. Consider previous response, adverse effects, comorbidity, interactions, cost, availability, route and the patient’s preference.
5. Obtain baseline information. Weight/BMI, pulse, blood pressure, glucose/HbA1c, lipids, renal/liver function, thyroid function, pregnancy status, ECG and movement examination when indicated.
6. Start low and review deliberately. Titrate according to response and tolerability; set a review date, outcome measure and stop or change plan.
7. Explain the medicine. State purpose, expected time to benefit, common effects, warning symptoms, missed-dose advice, interactions, alcohol advice, pregnancy advice and how to contact the service.

2. Pharmacodynamic and pharmacokinetic essentials

3. Antidepressants

Antidepressants are used for depressive disorders and selected anxiety, obsessive-compulsive, trauma-related, pain and eating disorders. They are not substitutes for risk management, psychosocial support or treatment of bipolar mania. Always ask about previous mania or hypomania, psychosis, substance use, suicide risk and medical causes before prescribing.

3.1 Selective serotonin reuptake inhibitors (SSRIs)

3.2 Serotonin–noradrenaline reuptake inhibitors (SNRIs)

Venlafaxine inhibits serotonin and noradrenaline reuptake in a dose-related manner. A common educational regimen is 37.5–75 mg/day initially, titrated to 75–225 mg/day. Monitor blood pressure, pulse, agitation, sexual effects, withdrawal and serotonin toxicity. Overdose may cause seizures, arrhythmia and severe toxicity.

Duloxetine is commonly started at 30 mg/day and increased to 60 mg/day; some indications use up to 120 mg/day. It may benefit neuropathic pain but requires caution in significant liver disease, heavy alcohol use, uncontrolled hypertension and interactions.

3.3 Tricyclic antidepressants (TCAs)

Amitriptyline, imipramine, clomipramine and nortriptyline block serotonin/noradrenaline reuptake but also antagonise muscarinic, histamine and alpha-1 receptors. They can be effective but are more dangerous in overdose.

• Indications: selected depression, OCD (especially clomipramine), neuropathic pain and migraine prevention depending on local guidance.
• Typical educational dosing: amitriptyline 25 mg at night, titrated cautiously (often 75–150 mg/day for depression; lower doses for pain); clomipramine 25 mg/day, titrated according to indication and specialist monitoring.
• Adverse effects: dry mouth, blurred vision, constipation, urinary retention, tachycardia, postural hypotension, sedation, weight gain, sexual dysfunction, seizures and arrhythmia.
• Contraindications/cautions: recent myocardial infarction, significant conduction disease, uncontrolled glaucoma, urinary retention, severe constipation, high suicide or overdose risk and interaction with MAOIs.
• Overdose emergency: wide QRS, hypotension, seizures, coma and ventricular arrhythmia require emergency toxicology management; do not manage with routine psychiatric observation.

3.4 Other antidepressants

• Mirtazapine: noradrenergic and specific serotonergic antidepressant. Start commonly at 15 mg at night, usual 15–45 mg/day. Sedation and appetite/weight gain are common; it may help insomnia or poor appetite but can worsen metabolic risk.
• Bupropion: noradrenaline/dopamine reuptake inhibition in some settings. Avoid or use specialist guidance in seizure disorder, eating disorders, abrupt alcohol/benzodiazepine withdrawal and interacting medicines.
• Moclobemide or other MAOIs: specialist use because of interaction and dietary/medicine precautions. Never combine with serotonergic medicines without an appropriate washout plan.

3.5 Antidepressant prescribing rules

• Screen for bipolarity before antidepressant monotherapy; antidepressant exposure can precipitate mania or rapid cycling in susceptible patients.
• Review early after initiation or dose change, especially where suicide risk, agitation, young age or limited support exists.
• Continue treatment for the recommended continuation period after remission and taper gradually when stopping.
• Explain discontinuation symptoms: dizziness, electric-shock sensations, irritability, anxiety, flu-like symptoms, insomnia and nausea.
• Avoid combining serotonergic medicines, linezolid, methylene blue, tramadol, lithium, St John’s wort or MAOIs without specialist review.

4. Antipsychotic medicines

Antipsychotics antagonise or modulate dopamine D2 receptors; many also affect serotonin, histamine, muscarinic and alpha-adrenergic receptors. They treat psychosis, schizophrenia, acute mania, severe agitation, psychotic depression and selected behavioural emergencies. Choose one antipsychotic, use the lowest effective dose, review response and avoid unnecessary polypharmacy.

4.1 First-generation and second-generation groups

4.2 Before and during antipsychotic treatment

• Baseline: diagnosis and target symptoms, weight/BMI, waist circumference, pulse, blood pressure, glucose/HbA1c, lipids, personal/family cardiac history, smoking/substances, pregnancy status where relevant, movement examination and ECG when indicated.
• Early follow-up: symptom response, adherence, sedation, orthostasis, akathisia, dystonia, suicidality, mania switch and emerging metabolic problems.
• Ongoing: weight, waist, blood pressure, glucose/HbA1c, lipids, movement symptoms, prolactin-related symptoms, sexual function, menstrual changes, cardiovascular risk and lifestyle support.
• Long-acting injections: confirm oral tolerability, product-specific loading and oral-overlap requirements, injection technique, renal/hepatic considerations and missed-injection plan.

4.3 Clozapine essentials

Clozapine is one of the most effective medicines for treatment-resistant schizophrenia and may reduce persistent suicidality, but it requires a specialist system. Obtain baseline and scheduled full blood counts according to the local programme. Educate about fever, sore throat, infection, severe constipation, abdominal pain, chest pain, breathlessness, palpitations, seizures, excessive sedation and sudden smoking changes. Treat constipation proactively; ileus can be fatal. Review interacting medicines, caffeine and smoking. Do not stop abruptly unless an emergency specialist plan is in place.

5. Mood stabilisers

5.1 Lithium

• Interactions increasing lithium: dehydration, low sodium intake, NSAIDs, ACE inhibitors/ARBs and thiazide or loop diuretics. Review any new medicine before use.
• Toxicity symptoms: worsening coarse tremor, vomiting/diarrhoea, ataxia, dysarthria, confusion, muscle weakness, hyperreflexia, seizures or reduced consciousness. Stop further doses only under urgent clinical guidance, obtain level and renal/electrolytes assessment, and arrange emergency care.
• Monitoring: weight/BMI, renal function, electrolytes including calcium and thyroid function at baseline and regularly; serum level after initiation or dose change and at clinically appropriate intervals. Take the sample at a consistent trough time according to local protocol.
• Patient advice: maintain steady fluid and salt intake, avoid dehydration, seek help during severe vomiting/diarrhoea or fever, do not self-medicate with NSAIDs, and never share tablets.

5.2 Valproate

Valproate increases central GABA availability and has effects on sodium channels and histone deacetylases. It can treat acute mania and prevent relapse in selected patients, but reproductive risks are major.

• Typical adult range: often 500–2000 mg/day, adjusted to response, tolerability and formulation; serum levels may support adherence or toxicity assessment but do not replace clinical review.
• Adverse effects: nausea, tremor, sedation, weight gain, hair changes, thrombocytopenia, hepatotoxicity, pancreatitis and hyperammonaemic encephalopathy.
• Contraindications/cautions: significant liver disease, mitochondrial disease, pancreatitis, bleeding disorder and pregnancy potential. Follow current national reproductive-safety rules; do not initiate in a person who could become pregnant unless specialist requirements and safer alternatives have been addressed.
• Interactions: lamotrigine toxicity and rash risk, aspirin/protein-binding effects, enzyme interactions and additive sedation.

5.3 Carbamazepine

Carbamazepine blocks voltage-gated sodium channels and is used for mania or selected seizure-related conditions. Start low and titrate; common adult total dosing is approximately 400–1600 mg/day according to indication and formulation.

• Monitor full blood count, liver function, sodium and clinical response.
• Adverse effects include dizziness, diplopia, ataxia, nausea, hyponatraemia, leukopenia, hepatic injury and serious skin reactions including Stevens–Johnson syndrome.
• It is a potent enzyme inducer: it can reduce oral contraceptive, antipsychotic, anticoagulant and antiretroviral concentrations. Check interactions carefully.

5.4 Lamotrigine

Lamotrigine inhibits voltage-gated sodium channels and glutamate release. It is valuable mainly for bipolar depression prevention rather than rapid control of mania. A common slow titration is 25 mg daily for two weeks, then 50 mg daily for two weeks, followed by gradual increases; exact schedules depend on interacting medicines.

• Never accelerate titration casually.
• Stop and urgently assess a widespread rash, mucosal lesions, fever, facial oedema or systemic symptoms.
• Valproate greatly increases lamotrigine exposure; enzyme inducers lower it. Pregnancy and contraception require specialist review.

6. Anxiolytics and hypnotics

6.1 Benzodiazepines

Diazepam, lorazepam, midazolam, clonazepam and related medicines enhance GABA-A inhibition. They can rapidly reduce severe anxiety, agitation, catatonia, seizures and alcohol withdrawal, but tolerance, dependence and respiratory depression make routine long-term use unsafe.

• Short-term educational examples: diazepam 2–5 mg once or twice daily; lorazepam 0.5–2 mg as needed under a defined plan. Alcohol withdrawal, seizures, procedural sedation and severe agitation use different protocols and monitoring.
• Adverse effects: sedation, falls, confusion, ataxia, memory impairment, paradoxical disinhibition and respiratory depression.
• Contraindications/cautions: severe respiratory disease, sleep apnoea, myasthenia gravis, severe hepatic failure, pregnancy, older age, concurrent opioids/alcohol and history of substance dependence.
• Withdrawal: anxiety, insomnia, tremor, perceptual disturbance, seizures and delirium. Taper gradually; abrupt cessation can be life-threatening.

6.2 Non-benzodiazepine options

• Buspirone: partial 5-HT1A agonist; useful for some generalised anxiety disorders, with delayed benefit and no rapid sedative effect. Typical starting dose 5–10 mg two or three times daily, titrated to 20–30 mg/day in divided doses.
• Hydroxyzine or sedating antihistamines: may cause short-term sedation but have anticholinergic and QT effects; avoid routine chronic use in older adults.
• Pregabalin: may help selected anxiety or neuropathic pain presentations; dizziness, oedema, weight gain, misuse and respiratory-depression risks require review.
• Sleep medicines: treat the cause of insomnia first. Sedative-hypnotics should be short-term, with a clear review and non-drug sleep plan.

7. Medicines in acute agitation, withdrawal and emergencies

Agitation is a symptom, not a diagnosis. Search for delirium, hypoxia, hypoglycaemia, intoxication, withdrawal, psychosis, mania, pain, urinary retention, trauma and medication toxicity. Use verbal de-escalation, a low-stimulation environment and the least restrictive intervention. If medication is required, follow local emergency protocols, check allergies and interactions, monitor airway, breathing, circulation, sedation, temperature and ECG where indicated, and document why it was necessary.

• Antipsychotic sedation: useful for psychotic or manic agitation but can cause dystonia, QT prolongation, hypotension, oversedation and NMS.
• Benzodiazepine sedation: useful for stimulant toxicity, alcohol withdrawal and seizures; avoid or monitor closely with opioids, respiratory disease, severe intoxication or delirium from unknown cause.
• Combination therapy: increases sedation, respiratory and cardiovascular risks; use only according to local protocol with adequate observation.

8. Recognising serious adverse drug reactions

9. Electroconvulsive therapy (ECT)

9.1 What ECT is

ECT is a planned medical procedure in which a controlled electrical stimulus produces a brief generalised seizure under general anaesthesia and muscle relaxation. Modern ECT is delivered by a trained multidisciplinary team with monitoring and resuscitation capability. The mechanism is multifactorial, involving network, neurotransmitter, neuroendocrine and plasticity changes; it is not adequately described as simply “resetting the brain.”

9.2 Indications

• Severe depression when rapid response is needed because of high suicide risk, refusal of food or fluids, severe psychomotor retardation, psychotic depression or life-threatening deterioration.
• Catatonia, especially malignant or medically dangerous catatonia.
• Severe mania or selected treatment-resistant psychosis when specialist assessment supports ECT.
• Depression that has not responded to adequate medication and psychological treatment, or where medicine is contraindicated or previously ineffective.

9.3 Pre-ECT assessment

• Confirm diagnosis, target symptoms, alternatives, previous treatment and expected benefit.
• Assess capacity and consent; explain voluntary and legally authorised pathways according to local law. Respect refusal unless a lawful emergency framework applies.
• Medical history: cardiovascular disease, arrhythmia, hypertension, aneurysm, raised intracranial pressure, seizures, pulmonary disease, pregnancy, anaesthetic history and current medicines.
• Physical examination, observations, airway assessment, ECG and targeted laboratory tests. Investigate unexplained neurological signs before proceeding.
• Review medicines that alter seizure threshold, blood pressure, cognition or anaesthetic risk. Anaesthesia and psychiatry teams decide what is withheld or continued.
• Record baseline cognition, mood/psychosis severity, function, risk and the patient’s goals so benefit and cognitive effects can be monitored.

9.4 Contraindications and precautions

There is no simple absolute contraindication for every patient, but uncontrolled raised intracranial pressure, unstable cardiovascular disease, recent major infarction, severe anaesthetic risk, significant aneurysm or other conditions may require optimisation, specialist consultation or alternative treatment. Pregnancy is not an automatic exclusion; severe illness may justify ECT with obstetric and anaesthetic planning.

9.5 Course, technique and aftercare

• ECT is usually given two or three times weekly; the number of treatments is individualised according to response and adverse effects.
• Electrode placement and stimulus parameters are chosen to balance speed, efficacy and cognitive burden. Bilateral treatment may act faster; unilateral treatment may reduce memory effects in some settings.
• Monitor airway, oxygenation, ECG, blood pressure, seizure duration, recovery and orientation. Ensure a responsible adult and safe transport after outpatient treatment.
• Common short-term effects include headache, muscle ache, nausea, confusion and transient memory impairment. Persistent or distressing memory problems require documentation, discussion and treatment review.
• Relapse prevention may include continuation medicine, psychological treatment, social support and, in selected recurrent severe illness, maintenance ECT under specialist care.

10. Psychotherapy and biological treatment work together

Medication should be integrated with psychoeducation, sleep and activity planning, family involvement, substance-use care, psychological therapy, occupational support and physical-health monitoring. Medicines reduce symptoms; they do not remove poverty, trauma, stigma, unsafe housing or social isolation. A good plan states how each intervention contributes to the patient’s recovery goals.

11. Monitoring checklist for every psychotropic prescription

12. Worked clinical cases

Case 1: Severe depression with reduced intake

A patient with severe depression has stopped eating, is psychotic and has active suicidal intent. Prioritise safety, medical assessment, hydration/nutrition and urgent specialist review. Rapid-acting treatment such as ECT may be considered when clinically appropriate. Do not wait weeks for a routine antidepressant response while life-threatening risk continues.

Case 2: New agitation after an antipsychotic

A patient paces constantly after a dose increase and says they feel unable to stay still. Consider akathisia rather than simply escalating the antipsychotic. Check suicide risk, review dose and interactions, examine for dystonia or NMS, and seek senior advice.

Case 3: Mania and antidepressant exposure

A patient treated for “recurrent depression” develops decreased need for sleep, grandiosity and risky spending after an antidepressant increase. Reassess the diagnosis, stop unsafe escalation, assess risk and consider a mood-stabilising strategy under specialist guidance. Antidepressant monotherapy is not a treatment for acute mania.

Case 4: Lithium and dehydration

A patient taking lithium develops vomiting and coarse tremor during diarrhoea. Treat as possible toxicity: urgent assessment, level with correct timing, renal function/electrolytes and medication-interaction review. Do not reassure the patient solely because the dose has not changed.

13. Examination and practice points

• SSRIs are often first-line for depression and anxiety, but screen for bipolar disorder and monitor early activation and suicide risk.
• Antipsychotic choice is a balance of efficacy, metabolic burden, movement effects, prolactin, sedation, QT risk, route, cost and patient preference.
• Lithium requires stable fluid/salt intake, renal and thyroid monitoring, interaction review and level timing.
• Valproate has major reproductive and hepatic safety implications; follow current national restrictions.
• Benzodiazepines are useful for selected short-term emergencies but create dependence, falls, respiratory depression and withdrawal risks.
• Serotonin syndrome and NMS are different emergencies: one follows serotonergic excess with clonus/hyperreflexia; the other follows dopamine blockade with rigidity, fever and autonomic instability.
• ECT is a consented anaesthetic procedure with rapid benefit in selected severe illness, not a punishment or last resort that must be delayed until every medicine fails.

14. Quick self-test

1. What must be screened for before antidepressant monotherapy?
2. Name five baseline domains to record before an antipsychotic.
3. Why is a tricyclic antidepressant dangerous in overdose?
4. List four factors that can raise lithium concentration.
5. What symptoms suggest neuroleptic malignant syndrome?
6. Why can abrupt benzodiazepine withdrawal be life-threatening?
7. What are three urgent indications for ECT?
8. How does smoking affect clozapine or olanzapine monitoring?
9. Why should antipsychotic polypharmacy be avoided unless clearly justified?
10. What should every medicine review document beyond the dose?

Answers

1. Past or current mania/hypomania, psychosis, substance-related symptoms, medical mimics and suicide risk.
2. Weight/BMI and waist, pulse/blood pressure, glucose/HbA1c, lipids, movement examination, cardiac history/ECG when indicated, pregnancy status, renal/liver function and current medicines.
3. It causes anticholinergic toxicity, seizures, hypotension, QRS widening and lethal arrhythmias at relatively small overdose quantities.
4. Dehydration, low sodium intake, NSAIDs, ACE inhibitors/ARBs and thiazide or loop diuretics.
5. Fever, severe rigidity, altered consciousness, autonomic instability and raised CK after dopamine blockade or related withdrawal.
6. Dependence and neuroadaptation can produce severe anxiety, delirium, seizures and autonomic instability when the medicine is stopped suddenly.
7. Life-threatening suicidal depression, refusal of food/fluids, psychotic depression, malignant catatonia or severe treatment-resistant mania are examples.
8. Polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2; stopping smoking can raise levels, while restarting can lower them. Monitor clinical state and consider levels where available.
9. It increases adverse effects, interactions, confusion about efficacy and difficulty attributing harm; use a single adequate trial unless specialist rationale is documented.
10. Target symptoms, benefit, adherence, adverse effects, risk, interactions, physical monitoring, patient preference, continuation/withdrawal plan and next review.

References and further reading

• NICE. Depression in adults: treatment and management.
• NICE. Psychosis and schizophrenia in adults: prevention and management.
• NICE. Bipolar disorder: assessment and management.
• WHO. mhGAP guideline for mental, neurological and substance use disorders, 2023.
• WHO. mhGAP Intervention Guide, version 2.0.
• NICE. Guidance on the use of electroconvulsive therapy.
• American Psychiatric Association. Electroconvulsive therapy patient and family information.
• Use current Uganda Clinical Guidelines, National Drug Authority information and local hospital protocols for prescribing, reproductive safety, monitoring, emergency sedation and ECT.