The CNS is a complex and only partially understood system, and despite knowing the principle chemical properties of many psychiatric drugs, speculating on their possible effects on brain function can be very difficult. Despite these limitations, it is important to know the underlying physiological systems mediated by the more common neurotransmitters.
Virtually all effective psychopharmacological drugs discovered to date were found by good luck, or by empiricism, that is, by probing disease mechanisms with a drug of known action but no prior proof that such actions would necessarily be therapeutic.
E.g. Chlorpromazine (first anti-psychotic, discovered in the 1950s – very potent but originally developed to be an anaesthetic), Amitriptyline (first anti-depressant, still widely used for neuropathic pain – no longer widely used as an anti-depressant because of its side effects).
The drugs which, act on the mental health conditions, work as agonists or antagonists of neurotransmitter receptors or less commonly as inhibiting regulatory enzymes (e.g. MOA inhibitors) that make or destroy neurotransmitters. Some drugs may compete with the neurotransmitter for its own binding site attempting to mimic the neurotransmitter or to block the neurotransmitter.
What are the key modulatory and transmission pathways pertinent to Psychiatric Disease?
Key transmission and modulatory pathways in the CNS – most pertinent to psychiatric disease include:
- Noradrenergic pathways (depression)
- Dopaminergic pathways (schizophrenia)
- Serotonergic (5-HT) pathways (depression)
- GABA-ergic pathways (anxiety)
- Cholinergic pathways (dementia)
- Glutamate Pathways (dementia)
What are the current models into the pathogenesis of mental health disorders?
Current models into the pathogenesis of mental health are contested and open to much development; however they appear to involve a mixture of genetic, biological, psychological, cultural and behavioural factors.
Genetic vulnerability to the expression of disease
Stressful life events (divorce, bereavement)
Individuals’ personality, coping skills, social support, how they’ve been brought up etc
Other environmental influences e.g. viruses, toxins, other diseases
BIOPSYCHOSOCIAL approach needed when considering aetiology and management. E.g. Biological: predisposing factors may be genetic, precipitating factors may be cannabis or other drugs and perpetuating factors may be non-compliance with anti-psychotic medication.
What are the symptoms of depression?
Depressive symptoms are common, and range from mild emotional changes to severe depression with delusions and hallucinations. The 3 core symptoms are low mood (feeling fearful, sad), anhedonia (lacking pleasure from anything, not enjoying the things you used to enjoy anymore) and decreased energy (gets tired easily, exhaustion). Secondary symptoms include hopelessness (depressive cognitions), reduced concentration, self harm, suicidal ideation, sleep disturbances, irritability and poor appetite are also quite common.
- Mild: 2/3 core + 2 secondary symptoms
- Moderate: 2/3 core + 3 secondary symptoms
- Severe: 3 core + 3+ secondary symptoms
- Need to have symptoms for 14 days
What is meant by unipolar and bipolar depression?
Unipolar depression is where the mood swing is always in the same direction. The majority of cases are due to external triggers such as difficult life events (reactive depression). However, about 25% of patients seem to have endogenous depression where no such relationship can be seen. This is often familial. Pharmacotherapy may be useful in either condition.
Bipolar affective disorder is characterised by depression and mania at different times in the course of the disease, and is considerably rarer.
Describe the Monoamine Hypothesis of Depression
There are many theories to the development of depression, the main one being the Monoamine Hypothesis of Depression. This states “Depression is caused by a deficiency of monoamine neurotransmitters in the brain, and mania is due to an excess.)
This arose from the observation that drugs that reduced NA and 5-HT (“monoamines”) led to lower mood (e.g. reserpine) and drugs that increased these monoamines improved mood (e.g. antidepressants). Note: the evidence is mixed
Describe the Neurotransmitter Receptor Hypothesis
Neurotransmitter Receptor Hypothesis:
An abnormality in the receptors for monoamine transmission leads to depression – e.g. depletion of receptors at the post-synaptic membrane, despite adequate neurotransmitter levels.
Deletion of neurotransmitter causes compensatory up-regulation of post-synaptic receptors – some post-mortem evidence
This is a gross simplification but appears to have some pharmacological basis. One weakness is that the biochemical changes these drugs cause take place immediately, but their therapeutic action may take several weeks to occur.
- Changes in receptor expression and density
- Altered balance of various neurotransmitter systems
- Long term adaptive responses – altered gene expressions, growth factors etc
However: there is no clear and convincing evidence that monoamine deficiency accounts for depression or that receptor change accounts for depression. There is growing evidence that despite apparently normal levels of monoamines and receptors, these systems do not respond normally.
Describe the Monoamine Hypothesis of Gene Expression
The Monoamine Hypothesis of Gene Expression
Deficiency in molecular functioning
Hypothesised problem within the molecular events distal to the receptor
What are the 4 main classes of antidepressants?
They are commonly used alongside CBT.
- Tricyclic Antidepressants (TCAs)
- Selective Serotonin Reuptake Inhibitors (SSRIs)
- Selective Serotonin/Noradrenaline Reuptake Inhibitors (SSNRIs)
- Monoamine Oxidase Inhibitors (MAOIs)
Nowadays, the vast majority of (new) patients with depression are treated with SSRIs and SSNRIs because of their improved safety profiles. However, there are still many people on TCAs both for depression and other indications. MAOIs are now rarely prescribed, but are important because of their potential for serious drug-drug and drug-food interactions.
Describe Selective Serotonin Reuptake Inhibitors
SSRIs are the first line therapy for any moderate to severe depression (with CBT) (any mild depression will have non-pharmacological agents used first, such as increased exercise, increased socialising etc) and examples include Fluoxetine, Citalopram, Sertraline or Paroxetine. They act by preventing the reuptake of serotonin by the presynaptic membrane, increasing the serotonin concentration in the synaptic cleft.
Citalopram is the most selective but prolong the QT interval (increased risk of Torsades and death), paroxetine is the most potent reuptake inhibitor (but patients struggle to stop)>
These drugs are almost completely absorbed from the gut, have long half lives (once daily dosage) and are metabolised by the liver. They are relatively well-tolerated by patients.The drugs are very safe in overdose (if on taken on own)
The main common ADRs are anorexia (due to reduced appetite), nausea and diarrhoea(normally settles 10-14 days later) as well as rare ones of mania (SSRIs can precipitate mania) and neurological side effects such as tremor, extrapyramidal syndromes. Possible increased suicidal ideation (thoughts and behaviours).
No therapeutic benefit seen until 4 weeks later. Motivation improves first, mood picks up later.
Need to review patient regularly, warn them of risk of suicide, make family aware.
What are the effects of TCAs? (Tricyclic Antidepressants)
First generation anti-depressants, still used but less often and not first line.
TCAs act by blocking both the re-uptake of serotonin and noradrenaline at the presynaptic membrane; examples include Amitriptyline or Clomipramine or Lofepramine. TCAs are absorbed by the gut, are lipid soluble, have long half-lives and are metabolised by the liver.
- Inhibition of noradrenaline uptake, resulting in enhanced nor-adrenergic neurotransmission (sympathomimetic effect).
- Muscarinic cholinoceptor blockade – reduced cholinergic neurotransmission (anticholinergic effect)
- Alpha 1-adrenoceptor blockade – suppression of noradrenergic neurotransmission (sympatholytic effect)
What are the side effects of TCAs?
However, due to their wide range of action as they affect lots of pathways, TCAs affect multiple systems and cause multiple side-effects so have limited clinical use. These range from CNS (sedation and impaired psychomotor function, lowering of seizure threshold), autonomic nervous system effects (reduced glandular secretions and eye accommodation block), CVS (tachycardia, postural hypotension and sudden cardiac effect – impair myocardial contractility) and GI (mainly constipation).
An amitriptyline overdose can be fatal – symptoms may include uneven heartbeats, extreme drowsiness, confusion, agitation, vomiting, hallucinations, feeling hot or cold, muscle stiffness, seizures or fainting. Sodium bicarbonate is a key treatment in amitriptyline and other tricyclic antidepressant toxicity.
Describe Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs)
These drugs were developed to cause reuptake of noradrenaline too, with examples including Venlafaxine and duloxetine; commonly used as second line/third line therapy – known as ‘pure’ non-selective monoamine uptake inhibitors.
Dose-dependent – lower doses serotonin action, high doses noradrenaline
They have the same ADRs as the SSRIs, as well as sleep disturbances, increased BP, dry mouth and hyponatraemia. Increases the risk of mania compared to SSRIs. They have a relatively short half life so may produce a withdrawal syndrome on discontinuation.
Monoamine Oxidase Inhibitors (MAOIs).
These are rarely prescribed now due to serious ADRs and DDIs – extremely cytotoxic.
Lots of possible interactions so need to avoid certain foods e.g. cheese
Schizophrenia is a common disabling psychiatric psychotic (psychosis is where patients are not in touch with reality) condition affecting about 1% of the UK population. You have approximately ~10% chance of getting it if one of your parents have it and a ~45-50% chance of getting it if both parents have schizophrenia. They die approximately 10-20 years younger than the general population but treatment can help them live independent or relatively independent lives. It is characterised by:
- Positive Symptoms: hallucinations (a perception in the absence of an external auditory – (or olfactory, visual, gustatory, tactile) stimulus), delusions (a fixed false belief that is out of keeping with someone’s culture or religious beliefs - often tend to be persecutory e.g. MI5 is out to get me), unusual speech-thought disorders (disturbances of thinking), abnormal behaviour (behavioural change), lack of insight
- Negative Symptoms: blunted affect, social withdrawal, poverty of thought and speech – unusual speech and thought, apathy, lack of self-care (won’t look after physical health etc. High rates of smoking, alcohol and substance misuse in schizophrenics).
- Cognitive Symptoms: selective attention, poor memory, reduced abstract thought
- Affective Symptoms: anxiety and depression
What can cause schizophrenia?
Schizophrenia has underlying genetic predispositions (having a strong familial component). There then appears to be multiple environmental insults that increase brain dysfunction (e.g. maternal gestational hypertension, viruses in utero). These repeated insults (also affected by upbringing) lead later to the phenotypical expression of schizophrenia. It is also a chronic condition often leading to significant neurodegenerative disease.
NB: Schizophrenia is an example of a mental illness with psychotic symptoms but psychotic symptoms may occur as a result of many conditions (e.g. infections, recreational and other drugs, metabolic abnormalities, severe depression, dehydration, delusional disorder, dementia, delirium) and in the short term may require similar treatments. However, these patients may or may not be schizophrenic.
What is the Dopamine Hypothesis?
Neurochemistry of Schizophrenia: several neurotransmitter theories have been put forward to explain the development of Schizophrenia and the rationale for therapeutic drug action. None are complete or fully explanatory. Best known is the dopamine hypothesis – where there is an excess of dopamine being released by the brain. The Dopamine Theory of Schizophrenia
Amphetamine (aka speed, whizz) causes symptoms very similar to positive symptoms of schizophrenia (delusions, hallucinations.
Dopamine antagonists are the best treatment for schizophrenia
Some evidence of increased dopamine function in schizophrenias.
- Amphetamine does not cause negative symptoms (not even long term misuse)
- Dopamine antagonists do not treat negative symptoms
- Changes in dopamine function may be a response to long term drug treatment (rather than being a core part of the disease).
Describe the main Dopamine pathways in the CNS
- Meso-limbic Pathways: important in emotional response and behaviour, and connect to the hippocampal and amygdala areas.
- Meso-cortical pathways: important in arousal and mood
- Nigrostriatal pathways: 75% of brain dopaminergic pathways. Important in the control of movement. Neurones span from the substantia nigra to the corpus striatum and is the key pathway damaged in Parkinson’s disease. Dopamine antagonism can thus induce “extra-pyramidal” movement disorders and are relevant to side effects of anti-psychotic drugs.
- Tubero-hypophyseal System: these are small pathways in the hypothalamus and pituitary gland –important with pituitary and hypothalamus function.
Describe antipsychotic medication
Antipsychotic medication: pharmacological treatment is primarily with anti-psychotic medication. These drugs are also sometimes referred to as major tranquilisers or neuroleptics. The main schizophrenia medication is D2 antagonism, meaning that the dopaminergic pathways are blocked, which can result in producing therapeutic responses, alongside enhanced negative and cognitive symptoms, potential dyskinesia and hyperprolactinaemia.
Describe typical antipsychotics
Typical anti-psychotics: these are the generally older treatments (first generation, 1950s) that tend to have increased dopamine (D2) antagonism producing extra-pyramidal side effects and tardive dyskinesia (difficult-to-treat and often incurable form of dyskinesia, a disorder resulting in involuntary, repetitive body movements – the involuntary movements are tardive, meaning they have a slow or belated onset – think horse eating, involuntary movement around the mouth or tongue – patient themselves have no physical sensation of this, aren’t aware, generally rreversible). These are the effects of D2 antagonism on the nigrostriatal pathway.
- D2 antagonism on the mesocortical pathway: enhanced negative and cognitive psychotic symptoms
- Mesolimbic pathway: dramatic therapeutic action on positive psychotic symptoms
- Tuberoinfundibular pathway: hyperprolactinaemia (lactation, infertility, sexual dysfunction).
Generally used less than atypicals for schizophrenia now but short term anti-psychotic use continues (haloperidol is used in an acute emergency setting for sedation and tranquilisation when necessary).
Older patients may still be on them.
Includes haloperidol (frequent EPS, low sedation), flupentixol (depot injection) and chlorpromazine (classical typical, sedating)
Is Schizophrenia associated with increased 5HT function?
5HT has been implicated in a number of behaviours which are disturbed in schizophrenia (e.g. perception, attention, mood, aggression, sexual drive, appetite, motor behaviour, sleep)
Many of the most effective antipsychotic drugs are antagonists at 5HT-2A receptors (Clozapine). NB: 5HT-2A receptor is thought to be the most involved in psychosis.
Precursors of 5-HT (e.g. tryptophan) exacerbate schizophrenia.
Is Schizophrenia associated with decreased cortical glutamate function?
Glutamate is the predominant excitatory neurotransmitter in the brain.
Phenycyclidine (PCP: angel dust: non-competitive antagonist at NMDA-type glutamate receptors) induces symptoms very similar to schizophrenia (both +ve and –ve symptoms)
Post mortem studies have shown increased cortical glutamate receptors and increased binding of glutamate receptor ligands in cortex, basal ganglia and hippocampal formation.
Glutamate systems are important but mechanism unclear – and we have not been able to develop a treatment that has a direct action on the glutamate system.
Describe the atypical antipsychotics
Atypical anti-psychotics: these are generally more modern (1990s) and most cause less extra-pyramidal side effects (EPS). These are increasingly the first-line treatments for new-onset schizophrenia for this reason. The differential effects are largely down to different receptor affinities and potency – these newer drugs have decreasing D2-receptor affinity and increasing 5-HT2 receptor affinity. However, they can all be highly effective treatments, though clozapine is thought to perhaps be the most effective. Unfortunately, its use is limited by serious adverse reactions.
Used mainly in schizophrenia rather than as short term anti-psychotics
Includes risperidone (classical typical, sedating), clopazine (highly efficacious, can cause agranulocytosis (1% - decreases neutrophils => infection => death), used in treatment-resistant cases but no depot preparation available, very close restrictions re prescription), quetiapine, olanzapine
Anti-psychotics can be oral (once or twice daily) and some of the drugs are available as depot preparations (tend to be more of the typical drugs) where injections lasts for 2-4 weeks. Depot preparations tend to be used for non-compliant patients or patients who refuse to take oral tablets.
NB: although atypical psychotics cause less EPS side effects than the typicals, they cause other side effects such as weight gain so not more effective or better than the typicals.
What are the effects of all atypical antipsychotics? Main ADRs?
All the anti-psychotics will produce sedation and tranquilisation within a few hours and the anti-psychotic effects will set in within a few days/weeks.
- Activating effect within weeks – negative symptoms (probably not the typicals)
- Production of extrapyramidal side effects – hours or days. Much less with the atypical antipsychotics.
The main ADRs of the anti-psychotics are excessive weight gain (especially Olanzapine), increased prolactin secretion (Ripseridone), extra-pyramidal side effects (less common with atypical anti-psychotics), postural hypotension and cardiac toxicity (causing long QT syndrome).
Atypical antipsychotics advantages: less EPSE side effects therefore more acceptable to patient (however do cause huge weight gain as satiety centre is affected => keep eating, so need to warn and advise patient about this, increases risk of diabetes and hypercholesterolaemia). Different preparations available e.g. dissolvable. Some once daily dosage.
Differing side effect profiles can be matched to patient characteristics (do they prefer weight gain or EPS)
Atypical antipsychotics are now the first-line treatment in schizophrenia, now as recommended by NICE.
Side effects of atypical antipsychotics vary between drugs, can have extrapyramidal side effects at high doses, weight gain, increased prolactin (e.g. risperidione) and sedation.
What can cause neuroleptic malignant syndrome? What is it?
Haloperidol safe in emergencies – patients acutely psychotic
- More sedating
- Well known side effects: EPS (parkinsonism, acute dystonia, akathasia (unable to keep or sit still), tardive dyskinesia
- Wide range of pharmacological action: dopamine receptor blockade, anticholinergic effects, alpha-adrenergic blockade, antihistamine effect
- NB: can cause neuroleptic malignant syndrome which is a medical emergency with a mortality rate ~10%. Symptoms include severe rigidity, hyperthermia, autonomic lability/instability (BP and temperature go up and down like a yoyo) and changes in level of consciousness. Treatment is to withdraw the antipsychotic + supportive treatment.
Other side effects can include postural hypotension, sedation, tachycardia, weight gain, endocrine changes e.g. prolactinaemia and pigmentation.
- Central Nervous System depression
- Cardiac toxicity – some prolong QTc more than others
- Risk of sudden death with high dose
The use of these antipsychotics in psychiatric diseases often crosses therapeutic boundaries as patients may have a combination of symptoms; for example anxiety symptoms in schizophrenic patients may merit dual therapy.
What is Anxiety? What are the principal neurotransmitters suspected to be involved in Anxiety?
Anxiety can be described as fear out of proportion of the situation, so that individuals undergo avoidance of the certain scenario or physical symptoms such as light-headedness, shortness of breath, hot and cold flushes, nausea, palpitations, numbness, pins and needles. Common fears include fear of dying, going crazy.
First line treatment for an anxiety disorder is non-pharmacological, commonly CBT (cognitive behavioural therapy – quite intense psychotherapy, exposure and response therapy – step-by-step approach). Treat any coexist disorder. Pharmacological agents can be used adjuncts in severe cases.
Principle Neurotransmitter Systems
- Serotonin (SSRIs are first line therapy for anxiety)
Describe the actions of BDZs
The main pharmacological treatment involved in anxiety disorders is the benzodiazepines (diazepam, temezepam, lorazepam), which act on the GABA receptors – bind to BDZ receptor and exert effects through structure known as GABA-BDZ receptor complex. There are 2 main groups of BDZ receptors – high and low affinity.
- High affinity group – important in anxiolytic, hypnotic and anticonvulsant effects of BDZs.
Inhibitory effects in brain.
These drugs also have a role in the acute management of seizures.
They act as full agonists at these receptor sites => enhance of GABA.
Bioavailability following oral administration is almost complete – maximum concentrations 30-90 minutes (work quickly)
Highly lipid soluble – CNS diffusion rapid.
Undergo renal excretion and have a long half life.
What are the side effects of BDZs and what could happen in overdose?
However, benzodiazepines are still rarely prescribed due to common side effects of significant dependence, drowsiness, dizziness and psychomotor impairment there is a toxic effect if taken during pregnancy. Occasional side effects include dry mouth, blurred vision, GI upset, ataxia, headache, reduced blood pressure. Rare side effects include amnesia, restlessness and rash.
? cleft lip and palate if used in pregnancy
If taken late in pregnancy may cause respiratory depression and feeding difficulties in baby
Treatment of overdose
- Deaths are rare – commonest cause is respiratory depression.
- Supportive treatment
- Any overdose can be treated by Flumazenil, which acts as a BDZ antagonist/partial inverse agonist on the GABA receptor. However flumazenil has a shorter half life than benzodiazepines so close monitoring is required – may have to give another dose later etc.
Why should you avoid prescribding BDZs? Why is it important to consider the toxicities of all of the drugs?
You should aim to avoid prescribing if possible or only prescribe short term (i.e. 1 week and not very often) as tolerance and dependence can occur.
Tolerance can occur i.e. need to increase the dose to achieve the same effect.
Dependence can happen after 2 weeks – on discontinuation of treatment can get withdrawal effects e.g. insomnia, agitation, anxiety
Overdoses: it is important as clinicians to understand thoroughly the toxicities of these drugs. This is for two reasons:
- Some are highly toxic in overdose (especially TCAs)
- Those prescribed them have a greater tendency to attempt suicide.
What is Bipolar Disorder? What are the treatment strategies?
Bipolar disorder is described as episodes of both mania and depression; mania (needs to occur for a week before diagnosis) includes feeling unusually excited, happy, optimistic or feeling irritably; overactive (on the go all the time); poor concentration and short attention span; poor sleep; rapid speech jumping from one idea to another; poor judgement (overspending); increased interest in sex (promiscuity, lack of disinhibition – leads to risk of STIs, HIV, unwanted pregnancy etc) and psychotic symptoms – hallucinations, grandiose delusions.
Mood stabilisers: lithium, sodium valproate, carbamazepine (really effective for treating rapid cycling between episodes), lamotrigine (really good for bipolar depression) and atypical antipsychotics (quite quick).
Avoid giving antidepressants (=> mood instability => trigger manic episodes).
What are the Lithium theories?
Electrolytes and channels – may compete with magnesium and calcium ions
Neurotransmitters – Lithium increases 5-HT, chronic lithium may reduce 5-HT receptor sites
Second messenger systems – lithium attenuates the effect of certain neurotransmitters on their receptors without altering receptor density.
Describe the therapeutic use of lithium
Lithium prevents both depression and mania and evidence suggests it reduces suicide.
Slow release preparations can be given once daily
Lithium levels need to be monitored (U&Es at least 3 monthly) and taken 12 hours after last oral dose – narrow therapeutic window
Need to check renal function and thyroid function before starting and every 6 months.
ACE inhibitors and NSAIDs can potentially increase the plasma concentration of lithium as could diarrhoea and vomiting, which could potentially be fatal
Uses of lithium
- Prophylaxis of mania and depression in bipolar disorder
- Augmentation of antidepressants in unipolar depression
- Good evidence for reducing suicidality
- Of all mood stabilisers, lithium has the best evidence.
What are the side of effects of lithium and signs of lithium toxicity?
Side effects include: memory and concentration problems, thirst, polyuria, tremor, drowsiness, weight gain (not as bad as antipsychotics) and acts as a nephrotoxin. It also can lead to endocrine changes such as hypothyroidism, hair loss and rashes.
If plasma lithium concentration starts to build up (hence need to monitor blood levels closely), toxic signs include vomiting, diarrhoea, coarse tremor, dysarthria, cognitive impairment, restlessness, agitation, confusion => ataxia => coma => death. REMEMBER lithium has a very narrow therapeutic window.
- Treatment of toxicity includes supportive measures, anticonvulsants, increase fluid intake/IV fluids etc, haemodialysis may be necessary.
Describe Dementia Medication
Dementia Medication (primary for Alzheimer’s) – slows down progression of disease (but not by that much – approximately gain an extra year at home before having to move to a care home)
Acetyl Cholinesterase Inhibitors
- Example: Donepezil, Galantamine, Rivastigmine
- Acetylcholine plays a role in arousal, memory, attention and mood.
- NICE guidance advices the medication to be available for mild and moderate dementia (was only moderately severe before).
- Slows down progression of Alzheimer’s Disease.
- Important side effects include: nausea, vomiting, anorexia, diarrhoea, fatigue, insomnia, bradycardia (can be profound if person is on Beta-blockers as well so monitor pulse before and after treatment), worsening of COPD, gastric/duodenal ulcers
- Memantine – licensed for moderate to severe dementia
- Usually well tolerated
- Common side effects include: hypertension, dyspnoea, headache, dizziness, drowsiness
Summary + What should I do next?
Psychopharmacology is a complex area
Drugs used alongside other treatments in psychiatry
Need patient centred approach to prescribing
Patient choice in selection of medication is also important
Psychoeducation – about illness and treatment including side effects
Extra notes for Schizophrenia:
Antipsychotics (neuroleptics) at high doses induce immobility and rigidity (neurolepsis), diminished arousal, sleep (major tranquilisers) and at low doses they are antipsychotic.
Therapeutic dose is more in line with a D2 receptor action (compared to D1) and clinical antipsychotic potency correlates with D2 affinity but not with D1 affinity.
Neurolepsis: psychomotor slowing, emotional quieting, affective indifference.
Dopamine D2 receptor antagonists cause neurolepsis therefore called neuroleptics.
Many newer antipsychotics do not cause neurolepsis – therefore best to use the term antipsychotic.
LOOK AT ADDITIONAL SLIDES LECTURE