Key points
- Psychopharmacology is the study of drugs that affect mood, thoughts, behaviour and sensation, and their use in treating psychiatric disorders.
- Pharmacokinetics is what the body does to the drug (absorption, distribution, metabolism, excretion). Pharmacodynamics is what the drug does to the body (receptors, dose-response, therapeutic index).
- Four dopamine pathways explain both the symptoms and the side effects: mesolimbic, mesocortical, tuberoinfundibular and nigrostriatal.
- Antidepressants take about 2 to 4 weeks to work. Lithium has a narrow therapeutic index and needs blood levels. Benzodiazepines are for short-term use because of dependence.
- Check special populations (children, pregnancy and lactation, medical illness, substance use), adherence, polypharmacy and stigma before and during any prescription.
Based on the MKU course outline for MBPS 4537, Introduction to Psychopharmacology (Year 4 Psychiatry). Doses are not given here: use the Kenya clinical guidelines and your hospital formulary when you prescribe.
1. What is psychopharmacology?
Psychopharmacology is the study of how drugs act on the nervous system to change mood, thinking, behaviour and sensation, and how those drugs are used to treat psychiatric disorders.
Principles of drugs acting on the nervous system
- A drug must reach its target in the brain, so it has to cross the blood-brain barrier (lipid-soluble drugs cross easily).
- Most psychotropic drugs act on neurotransmitter systems: they change release, reuptake, breakdown or receptor activity.
- The first effect on a receptor is quick, but the clinical benefit often takes weeks, because the brain adapts.
- Every drug has wanted and unwanted effects. Side effects usually come from the same receptors, in other pathways.
2. Pharmacokinetics: what the body does to the drug
| Step | What happens | Why it matters in psychiatry |
|---|---|---|
| Absorption | The drug enters the blood: oral, intramuscular, intravenous, or a long-acting depot injection. Oral drugs go through the liver first (first-pass metabolism). | Intramuscular and depot injections help in agitation and when adherence is poor. |
| Distribution | The drug moves to tissues, bound partly to plasma proteins. Lipid-soluble drugs cross the blood-brain barrier and accumulate in fat. | Highly protein-bound drugs can interact; fat-soluble drugs (such as diazepam) act longer in older and obese patients. |
| Metabolism | Mainly in the liver by cytochrome P450 (CYP) enzymes, such as CYP2D6, CYP3A4, CYP1A2 and CYP2C19. | Inhibitors raise drug levels (for example fluoxetine and paroxetine inhibit CYP2D6). Inducers lower them (for example carbamazepine, rifampicin). Smoking induces CYP1A2 and can lower olanzapine and clozapine levels. |
| Excretion | Mainly by the kidney (lithium is excreted unchanged) or bile. | In kidney disease lithium accumulates and becomes toxic. |
Half-life tells you how long a drug lasts. A drug reaches steady state after about 5 half-lives, so a change in dose shows its full effect only after that time.
3. Pharmacodynamics: what the drug does to the body
- Agonist: binds a receptor and activates it.
- Antagonist: binds a receptor and blocks it (haloperidol blocks dopamine D2 receptors).
- Partial agonist: activates the receptor, but less than the natural transmitter. Aripiprazole is a partial agonist at D2 receptors and buspirone is a partial agonist at 5-HT1A receptors.
- Complete or full agonist: produces the maximum response of the receptor.
- Dose-response: a larger dose gives a larger effect, up to a plateau, and more side effects.
- Therapeutic index: the gap between the effective dose and the toxic dose. A narrow index (lithium) needs blood level monitoring. A wide index (most SSRIs) is safer in overdose.
4. Neurobiology: neurons and synapses
Structure of a neuron: dendrites receive signals, the cell body (soma) integrates them, the axon carries them, and the axon terminal releases neurotransmitter.
The synapse:
- An electrical signal reaches the axon terminal.
- Neurotransmitter is released into the synaptic cleft.
- It binds receptors on the next neuron and changes its activity.
- The signal ends when the transmitter is taken back by reuptake transporters, or broken down by enzymes (such as monoamine oxidase, MAO).
Most psychotropic drugs work at this point: they block reuptake (SSRIs), block receptors (antipsychotics), block breakdown (MAO inhibitors) or enhance receptor action (benzodiazepines).
5. Neurotransmitters
| Transmitter | Main role | Link to psychiatry and drugs |
|---|---|---|
| Dopamine | Reward, motivation, movement, thinking | Excess activity in some pathways is linked to psychosis. Antipsychotics block D2 receptors. |
| Serotonin (5-HT) | Mood, sleep, appetite, anxiety | SSRIs raise synaptic serotonin. Many second-generation antipsychotics block 5-HT2A. |
| Norepinephrine | Alertness, arousal, mood | SNRIs and atomoxetine raise it. |
| GABA | Main inhibitory transmitter | Benzodiazepines enhance GABA-A receptor action: sedation, anxiolysis, anticonvulsant effect. |
| Glutamate | Main excitatory transmitter | Involved in schizophrenia (NMDA receptor hypofunction) and in learning and memory. |
| Acetylcholine | Memory, attention, autonomic function | Nicotinic receptors are ion channels; muscarinic receptors are G-protein coupled. Blocking muscarinic receptors causes dry mouth, constipation and blurred vision. |
| Histamine | Wakefulness | Blocking H1 receptors causes sedation and weight gain. |
| Neuropeptides | Modulate other transmitters (for example endorphins, oxytocin, substance P) | Involved in pain, stress and social behaviour. |
6. The four dopamine pathways
| Pathway | Function | If activity is high | If a drug blocks D2 receptors here |
|---|---|---|---|
| Mesolimbic | Reward and salience | Positive symptoms of psychosis (hallucinations, delusions) | Positive symptoms improve (the aim of treatment) |
| Mesocortical | Cognition, motivation, emotion | Low activity is linked to negative and cognitive symptoms | Negative symptoms may not improve or may worsen |
| Tuberoinfundibular | Dopamine inhibits prolactin release from the pituitary | Hyperprolactinaemia (galactorrhoea, menstrual disturbance, sexual dysfunction) | |
| Nigrostriatal | Control of movement | Extrapyramidal side effects (dystonia, akathisia, parkinsonism, tardive dyskinesia) |
Exam tip: link each pathway to one symptom and one side effect. Mesolimbic = positive symptoms; mesocortical = negative symptoms; tuberoinfundibular = prolactin; nigrostriatal = movement disorders.
7. Effects of psychotropic drugs: short term and long term
| Short term | Long term | |
|---|---|---|
| What happens | Receptor effects begin within hours, with early side effects (sedation, nausea, agitation) | The brain adapts over weeks, and the clinical benefit appears |
| Examples | SSRIs may cause anxiety and nausea in week 1; antipsychotics sedate and calm agitation quickly | Antidepressant response takes about 2 to 4 weeks; antipsychotics need weeks for psychotic symptoms; long-term risks are weight gain and metabolic syndrome, tardive dyskinesia, tolerance and dependence (benzodiazepines), and discontinuation symptoms |
8. Antidepressants
Theories. The monoamine hypothesis says depression involves low serotonin, norepinephrine and dopamine function. The inflammatory hypothesis links depression with raised inflammatory markers and immune activation. Neither explains everything, and the delay before benefit suggests the brain adapts over time.
| Class | Examples | Mechanism | Points to remember |
|---|---|---|---|
| SSRIs | Fluoxetine, sertraline, paroxetine, escitalopram | Block the serotonin transporter | First-line for depression and anxiety. Nausea, sexual dysfunction, insomnia or agitation at first, hyponatraemia (especially in older patients), increased bleeding risk. Paroxetine has the worst discontinuation symptoms. Fluoxetine has a long half-life. |
| SNRIs | Venlafaxine, duloxetine | Block serotonin and norepinephrine reuptake | Can raise blood pressure (venlafaxine, dose-dependent). Nausea, sweating. Duloxetine also helps neuropathic pain. |
| Atypical antidepressants | Bupropion | Blocks dopamine and norepinephrine reuptake | Lowers the seizure threshold; little sexual dysfunction; used in smoking cessation. |
| Trazodone | 5-HT2A antagonist and weak reuptake blocker | Sedating; priapism is a rare risk. | |
| Mirtazapine | Blocks alpha-2, 5-HT2 and H1 receptors | Sedating, increases appetite and weight. | |
| Vortioxetine | Multimodal serotonergic action | Nausea is the commonest side effect. |
Safety points
- Serotonin syndrome: agitation, sweating, tremor, clonus, hyperthermia. It follows combining serotonergic drugs (for example an SSRI with an MAO inhibitor, tramadol or linezolid).
- In young people, watch for suicidal thoughts when starting an antidepressant.
- Do not stop suddenly: taper, to avoid discontinuation symptoms.
9. Antipsychotics
Underlying theory. The dopamine hypothesis says excess dopamine activity in the mesolimbic pathway produces positive symptoms. The glutamate hypothesis says reduced NMDA receptor function contributes to positive, negative and cognitive symptoms.
First-generation antipsychotics (FGAs)
- Examples: haloperidol, fluphenazine, chlorpromazine.
- Mechanism: block D2 receptors.
- High-potency drugs (haloperidol, fluphenazine) cause more extrapyramidal side effects. Low-potency chlorpromazine is more sedating, with anticholinergic effects and postural hypotension.
- Other effects: hyperprolactinaemia, QT prolongation, neuroleptic malignant syndrome (fever, rigidity, altered consciousness, raised creatine kinase), tardive dyskinesia with long use.
- Fluphenazine and haloperidol are available as long-acting depot injections.
Second-generation antipsychotics (SGAs)
- Examples: olanzapine, risperidone, quetiapine, lurasidone.
- Mechanism: block D2 and 5-HT2A receptors.
- Fewer extrapyramidal effects at usual doses, but more metabolic effects.
| Drug | Notable adverse effects |
|---|---|
| Olanzapine | Marked weight gain, diabetes and lipid changes, sedation |
| Risperidone | Hyperprolactinaemia, extrapyramidal effects at higher doses |
| Quetiapine | Sedation, postural hypotension, weight gain |
| Lurasidone | Less weight gain; nausea and akathisia; take with food |
Monitor weight, waist, blood pressure, glucose or HbA1c and lipids, and ask about movement symptoms.
10. Anxiolytics and hypnotics
- Benzodiazepines (diazepam, clonazepam, alprazolam) enhance GABA-A receptor action. They are fast acting and effective for acute anxiety, agitation, alcohol withdrawal, seizures and catatonia.
- Problems: sedation, falls, memory impairment, tolerance, dependence and withdrawal (including seizures after sudden stopping), and respiratory depression with alcohol or opioids. Use the lowest dose for the shortest time.
- Non-benzodiazepine hypnotics (zolpidem, zopiclone) act at the GABA-A receptor too and are for short-term insomnia. They can also cause dependence and complex sleep behaviours.
- Buspirone is a 5-HT1A partial agonist for generalised anxiety. It works slowly, over weeks, and does not cause dependence or sedation.
11. Mood stabilisers
Lithium
- The classic mood stabiliser for bipolar disorder (prevention and mania).
- Narrow therapeutic index: measure blood levels about 12 hours after the last dose, and check kidney function, thyroid function and calcium.
- Side effects: tremor, thirst and polyuria, weight gain, hypothyroidism, kidney damage with long use.
- Toxicity: vomiting and diarrhoea, coarse tremor, ataxia, confusion, seizures.
- Levels rise with dehydration, NSAIDs, ACE inhibitors and thiazide diuretics.
- Risk in pregnancy (cardiac malformations).
Anticonvulsants used as mood stabilisers
| Drug | Notes |
|---|---|
| Valproic acid | Effective in mania. Teratogenic (neural tube defects): avoid in women who can become pregnant. Weight gain, tremor, liver toxicity, pancreatitis. |
| Carbamazepine | Mania and prevention. Strong CYP enzyme inducer, so it lowers levels of many drugs. Hyponatraemia, rash (HLA-B*1502 risk of Stevens-Johnson syndrome in some Asian populations), blood count changes. |
| Lamotrigine | Prevents bipolar depression. Titrate slowly: rash can progress to Stevens-Johnson syndrome. |
12. ADHD medication
- Stimulants: methylphenidate raises dopamine and norepinephrine by blocking their reuptake. Works within hours. Side effects: reduced appetite, insomnia, increased heart rate and blood pressure, slowed growth in children (monitor height and weight), potential for misuse.
- Non-stimulants: atomoxetine is a selective norepinephrine reuptake inhibitor. Takes weeks to work, with no misuse potential. Side effects: nausea, reduced appetite, sleepiness, and rarely liver injury. Watch for suicidal thoughts, especially in children and adolescents.
13. Special populations
| Group | Points to consider |
|---|---|
| Children and adolescents | Few drugs are licensed for them; start low and go slow; monitor growth. Watch for suicidal thoughts when starting an antidepressant. Psychological therapy is often tried first. |
| Pregnancy and lactation | Weigh the risk of untreated illness against the risk to the baby. Avoid valproate. Lithium and carbamazepine carry risks. Paroxetine is usually avoided in pregnancy. Benzodiazepines late in pregnancy can affect the newborn. Sertraline is commonly preferred during breastfeeding. Refer early for specialist advice. |
| Medically ill patients | Adjust for kidney and liver disease; check heart disease and QT prolongation; consider interactions with other drugs. |
| Substance use disorder | Benzodiazepines can be misused and are dangerous with alcohol and opioids. Bupropion lowers the seizure threshold, a problem in alcohol withdrawal. Treat withdrawal and intoxication first. |
14. Cultural and ethnic considerations
- Explain the illness and the medicine in language the patient and family understand.
- Ask about traditional or herbal remedies, faith-based care and substance use such as khat that may affect treatment or interact with drugs.
- Beliefs about mental illness (for example spiritual causes) affect whether people accept and keep taking medicine. Respect them, and work with the family and, where appropriate, religious or traditional leaders.
- Enzyme activity differs between ethnic groups, so dose needs and side effects can differ.
15. Treatment adherence and compliance
- Many patients stop psychiatric drugs, because of side effects, poor insight, cost, a complicated regimen, stigma, or because they feel better.
- Improve adherence with simple regimens (once daily if possible), psychoeducation for the patient and family, early review of side effects, long-acting depot injections where suitable, and a good therapeutic relationship.
- Always ask about missed doses without blame.
16. Polypharmacy
- Polypharmacy is the use of more drugs than are clinically needed.
- It increases side effects, interactions, cost and non-adherence.
- Prefer one drug at an adequate dose for an adequate time; review every drug regularly and stop those without a clear benefit.
17. Stigma and patient education
- Stigma about "mental" drugs makes people hide treatment or stop it. Explain that these are medicines for an illness, like those for hypertension or diabetes.
- Teach the patient and family: what the drug is for, how long it takes to work, the common side effects, what to do about missed doses, not to stop suddenly, and when to return. Correct myths such as "all these drugs are addictive".
Drugs at a glance
| Class | Examples | Key warning |
|---|---|---|
| SSRIs | Fluoxetine, sertraline, paroxetine, escitalopram | Hyponatraemia, serotonin syndrome, discontinuation |
| SNRIs | Venlafaxine, duloxetine | Raised blood pressure |
| Atypical antidepressants | Bupropion, trazodone, mirtazapine, vortioxetine | Seizures (bupropion), sedation and weight gain (mirtazapine) |
| First-generation antipsychotics | Haloperidol, fluphenazine, chlorpromazine | Extrapyramidal effects, NMS |
| Second-generation antipsychotics | Olanzapine, risperidone, quetiapine, lurasidone | Metabolic syndrome, prolactin (risperidone) |
| Benzodiazepines | Diazepam, clonazepam, alprazolam | Dependence, respiratory depression |
| Non-benzodiazepine hypnotics, buspirone | Zolpidem, zopiclone, buspirone | Short-term use; buspirone is slow |
| Mood stabilisers | Lithium, valproic acid, carbamazepine, lamotrigine | Lithium toxicity, valproate teratogenicity, lamotrigine rash |
| ADHD drugs | Methylphenidate, atomoxetine | Appetite and growth, misuse; suicidality (atomoxetine) |
Practice questions
1. Define psychopharmacology. The study of drugs that affect mood, thoughts, behaviour and sensation, and their use in treating psychiatric disorders.
2. What is the difference between pharmacokinetics and pharmacodynamics? Pharmacokinetics is what the body does to the drug: absorption, distribution, metabolism and excretion. Pharmacodynamics is what the drug does to the body: receptor action, dose-response and therapeutic index.
3. What is the therapeutic index, and which psychiatric drug has a narrow one? The gap between the effective dose and the toxic dose. Lithium has a narrow therapeutic index, so blood levels are monitored.
4. Name the four dopamine pathways and one effect of each. Mesolimbic (positive symptoms of psychosis), mesocortical (negative and cognitive symptoms), tuberoinfundibular (blockade causes hyperprolactinaemia) and nigrostriatal (blockade causes extrapyramidal effects).
5. How long do antidepressants take to work? Usually about 2 to 4 weeks, because the brain adapts to the drug over time.
6. Give two examples each of SSRIs and SNRIs. SSRIs: fluoxetine, sertraline, paroxetine, escitalopram. SNRIs: venlafaxine and duloxetine.
7. What is the main mechanism of action of benzodiazepines? They enhance GABA-A receptor action, increasing inhibition. This gives sedation, anxiolysis and an anticonvulsant effect.
8. List three factors that raise lithium levels. Dehydration, NSAIDs, ACE inhibitors and thiazide diuretics (any three), and kidney disease.
9. Which mood stabiliser should be avoided in women who can become pregnant, and why? Valproic acid, because it is teratogenic (neural tube defects).
10. What is polypharmacy, and why is it a problem? Using more drugs than are clinically needed. It raises side effects, interactions, cost and non-adherence.
Exam-style MCQs with answers and explanations
Try each question before you open the answer.
1. Which dopamine pathway is responsible for hyperprolactinaemia when D2 receptors are blocked?
A. Mesolimbic
B. Mesocortical
C. Tuberoinfundibular
D. Nigrostriatal
Answer: C. Dopamine normally inhibits prolactin release from the pituitary through the tuberoinfundibular pathway. Blocking D2 receptors there raises prolactin.
2. Parkinsonism, dystonia and akathisia after starting haloperidol are caused by blockade in which pathway?
A. Nigrostriatal
B. Mesolimbic
C. Tuberoinfundibular
D. Mesocortical
Answer: A. The nigrostriatal pathway controls movement. D2 blockade there causes extrapyramidal side effects.
3. Which drug is a partial agonist at the 5-HT1A receptor and does not cause dependence?
A. Diazepam
B. Buspirone
C. Zolpidem
D. Alprazolam
Answer: B. Buspirone is a 5-HT1A partial agonist that works slowly and does not cause dependence.
4. A patient on lithium develops vomiting, diarrhoea, coarse tremor and ataxia after starting ibuprofen. What is the most likely explanation?
A. Serotonin syndrome
B. Neuroleptic malignant syndrome
C. Lithium toxicity
D. Tardive dyskinesia
Answer: C. NSAIDs reduce the kidney clearance of lithium and raise its level. Vomiting, diarrhoea, coarse tremor and ataxia are signs of toxicity.
5. Which antipsychotic is most associated with marked weight gain and metabolic syndrome?
A. Haloperidol
B. Lurasidone
C. Olanzapine
D. Fluphenazine
Answer: C. Olanzapine causes the most weight gain and metabolic disturbance of this group. Monitor weight, glucose and lipids.
6. Which mood stabiliser needs slow dose titration because of the risk of a serious rash?
A. Lamotrigine
B. Carbamazepine
C. Valproic acid
D. Lithium
Answer: A. Lamotrigine rash can progress to Stevens-Johnson syndrome, so the dose is raised slowly.
7. Which antidepressant lowers the seizure threshold and is also used for smoking cessation?
A. Mirtazapine
B. Bupropion
C. Sertraline
D. Trazodone
Answer: B. Bupropion blocks dopamine and norepinephrine reuptake, lowers the seizure threshold and helps in smoking cessation.
8. A woman with bipolar disorder who may become pregnant needs a mood stabiliser. Which should be avoided?
A. Lamotrigine
B. Valproic acid
C. Quetiapine
D. Olanzapine
Answer: B. Valproic acid is teratogenic and is avoided in women who can become pregnant.
9. Which of the following is the non-stimulant ADHD medicine?
A. Methylphenidate
B. Atomoxetine
C. Lithium
D. Buspirone
Answer: B. Atomoxetine is a selective norepinephrine reuptake inhibitor. Methylphenidate is the stimulant.
10. After how many half-lives does a drug reach steady state?
A. 1
B. 2
C. 5
D. 10
Answer: C. A drug reaches steady state after about 5 half-lives, so the full effect of a dose change shows after that time.
References
- Mount Kenya University, School of Medicine. Psychiatry and Mental Health MBChB Curriculum, Year 4, unit MBPS 4537, Introduction to Psychopharmacology.
- Schatzberg's Manual of Clinical Psychopharmacology, 10th edition. 2024.
- Semple D, Smyth R. Oxford Handbook of Psychiatry. 4th ed. Oxford University Press; 2019.
- Republic of Kenya, Ministry of Health. National Clinical Guidelines for Management of Common Mental Disorders. 2025.