Psychopharmacology of Schizophrenia

What are the positive symptoms of Schizophrenia?

Hallucinations, delusions, thought disorder, paranoia

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What are the negative symptoms of Schizophrenia?

Lack of motivation, social withdrawal, apathy, anhendonia

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What are the neurocognitive impairment symptoms of Schizophrenia?

Attention, memory, executive function

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Describe general features of Schizophrenia

Chronic illness, equal gender incidence, age of onset 20-39 years old, later onset in women, decrease 15-20 years in life expectancy, difficult to get employment, stigma (recommendations - prescribing, pharmacist, appropriate diagnosis)

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What are the names of the two manuals used to diagnose patients with Schizophrenia?

International Classification of Diseases (10th Revision, UK) and Diagnostic and Statistical Manual of Mental Disorders (5th Edition, US)

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What are the causes of Schizophrenia?

Multifactorial - cannabis, environment, stress, genetic (high risk in twins, 1 in 2), lifestyle

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What are the other contributing factors to the cause of Schizophrenia?

Environmental - stress, life events, socioeconomic class, family problems. Developmental - problems during birth, viral infection during early months of pregnancy affecting development. Social - cannabis doubles risk of Schizophrenia, migration

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Which pathways in brain are affected in people with Schizophrenia?

Mesolimbic dopamine pathway and mesocorticol dopamine pathway - dopamine theory

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What are the two types of antipsychotics?

Typical (older, conventional, first generation, FGAs) and Atypical (newer, second generation, SGAs)

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Outline the mechanism of action of drugs

Dopamine stimulates D2 receptors causing an increase in dopamine activity. Antipsychotic activity is achieved by blocking dopamine at D2 receptors. 5-HT (serotonin) is involved

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What is the aim of drug treatment?

Improve symptoms and prevent relapse and readmission (role as pharmacist - maximise benefit and minimise side effects)

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What is the effect of antipsychotics?

Initial response ~ 1-2 weeks, full effect of dosage change ~ 2 weeks, full effect of antipsychotic ~ 4-6 weeks, some patients get better with 1st antipsychotic, some required 2nd drug, some are treatment resistant

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What is the ideal Schizophrenia treatment pathway?

Antipsychotic 1 - antipsychotic 2 - clozapine

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What are the issues with the ideal Schizophrenia treatment pathway?

Medicine adherence, side effects, slow onset of antipsychotics

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Describe features of typical vs atypical antipsychotics?

Typicals - generally cheaper, EPSE, increases prolactin. Atypicals - sometimes more expensive (if no generic available), weight gain, diabetes, dyslipidaemia, metabolic syndrome

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Give examples of typical antipsychotics

Phenothiazines (chlopromazine, trifluoperazine). Butyrophenones (haloperiodol). Sulpiride. Thioxanthenes (flupentixol/depixol, zuclopenthixol/clopixol)

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Give examples of Extra Pyramidal Side Effects

Dystonia, akathisia, pseudo-parkinsonism, tardive dyskinesia

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What are the effects of hyperprolactinaemia?

Sexual dysfunction, amenorrhoea, galactorrhoea, anovulation, gynaecomastia, osteoporosis (reduced bone material density), increased risk of breast cancer

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What is prolactin?

Dopamine (D2) blockade hypothalamus. Hormone synthesised and stored in anterior pituitary gland. Stimulates milk production and production of progesterone in the ovary. Under the inhibitory control of dopamine

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Which mechanisms are involved in weight gain as a side effect?

5-HT2C antagonism, H1 antagonism, hyperprolactinaemia, increased serum leptin. No evidence that drugs exert metabolic effect, weight gain is a result of increased food intake and reduced energy expenditure

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What are the suggested mechanisms for diabetes as a side effect?

5-HT2A/2C antagonism, increased plasma lipids, weight gain, leptin resistance. Risk is higher for younger adults and clozapine/olanzapine patients

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Describe features of Dylipidaemia

FGAs increased cholesterol and TG. SGAs increase cholesterol and TG (+++). Obesity, diabetes, increased risk of CVD

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Describe features of metabolic syndrome

Syndrome X. Central obesity, high blood pressure, high triglycerides, low HDL-cholesterol, insulin resistance

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Describe other adverse effects (1)

H1 histamine antagonist (sedation, weight gain e.g. chlorpromazine, quetiapine, olanzapine, clozapine). Alpha 1 adrenergic antagonist (postural hypotension, sexual dysfunction e.g. risperidone, clozapine)

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Describe other adverse effects (2)

Antimuscarinic, ACh (dry mouth, blurred vision, constipation, urinary retention e.g. chlorpromazine, clozapine)

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Describe features of sudden death

Sudden cardiac death. Incidence 1 in 1000. 3-fold increase with AP

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What is the possible mechanism for sudden death

Prolongation of QTc (ECG). Complex numerous mechanisms involving K, Na and Ca

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Describe features of neuroleptic malignant syndrome

Rare but potentially fatal. Difficult diagnose. Signs/symptoms: elevated CK, disphoresis, fever, fluctuating BP, muscle rigidity/severe muscle spasms, fluctuating consciousness, confusion, tachycardia

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Describe features of treatment resistant Schizophrenia?

Little/no response to at least two antipsychotics (is it a different in itself?). Drug of choice is clozapine - superior for positive and negative symptoms

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Describe features of Clozapine

Unlikely to cause EPSE, no effect on prolactin but sedating, weight gain/diabetes +++, hypersalivation, myocarditis, seizures, pneumonia

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Describe features of important monitoring of Clozapine (constipation)

Affects 80% of patients, slows gut motility, can be fatal (bowel obstruction leads to necrosis or sepsis), establish baseline and monitor bowel habit

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Describe features of important monitoring of Clozapine (agranulocytosis)

Affects <1% of patients, every patient on treatment has regular full blood count (FBC), WCC and neutrophils monitored. Main rule - no 'green' blood = no clozapine supply

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Describe features of NICE guidance (1)

Joint decisions made by HCP/patient. For newly diagnosed patients with Schizophrenia offer oral antipsychotic medication (FGA or SGA). Provide info/benefits of each drug. Offer ECGs where required. Antipsychotics should not be regularly co-prescribed

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Describe features of NICE guidance (2)

Consider depot if preferred by patient or if non-compliant. Offer clozapine in TRS

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What are the main points about treating patients with Schizophrenia? (1)

Best treatment mean balancing efficacy and tolerability for individual patient. Metabolic side effects are under reported/treated so be proactive and vigilant for signs of potentially fatal side effects. Adherence is improved by talking to patients

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What are the main points about treating patients with Schizophrenia? (2)

Reassure patients that many side effects can be managed. Use clozapine if patient is treatment resistant. Remember that every time a patient relapses they have a reduced chance of full recovery

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Psychopharmacology of Schizophrenia

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