29th January 2024

Management

All patients with an acute episode of Schizophrenia should be started on antipsychotic medications to minimise their symptoms, induce remission and return them to normal functioning. The choice of antipsychotic should follow a discussion with the patient regarding current symptoms, side effects and alternative treatments. The management plan should follow the ‘BioPsychoSocial’ model.

• Biological: Drug therapy
• Psychological: supportive therapy, cognitive behavioural therapy, family therapy
• Social: Avoid drugs/alcohol, increase social support (Community Psychiatric Nurse support), stable housing, financial support and employment

There are two classes of antipsychotics commonly used in schizophrenia: First-Generation Antipsychotics (FGA) and Second-Generation Antipsychotics (SGA). In recent years, SGA has been the preferred choice due to carrying a lower risk of extrapyramidal side effects; however, there is no difference noted between the efficacy of FGA and SGA in treatment of negative and cognitive symptoms of schizophrenia (aside from Clozapine). An antipsychotic should be trialled for a minimum of four weeks before considering alternative options due to poor response.

First-Generation Antipsychotics (FGAs)

FGAs are primarily dopamine antagonists, blocking the action of dopamine on its receptors throughout the brain. One of the theoretical causes of schizophrenia is excess dopamine in the mesolimbic pathways, which is associated with positive symptoms; hence, blocking this pathway aids in alleviating positive symptoms like hallucinations and delusions. However, FGAs are not specific to D2 receptors and exhibit their action on a number of other receptors, resulting in a varied side effect profile. This includes exerting antagonism at Acetylcholine ACh M1, Histamine H1 antagonist and a1-adrenergic receptors.

Source: Adapted from: UpToDate. First Generation Antipsychotic Medications: Pharmacology, administration and comparative side effects [internet]. 2022 [cited 2022 July 15]. Available from: https://www.uptodate.com/contents/first-generation-antipsychotic-medications-pharmacology-administration-and-comparative-side-effects

Second-Generation Antipsychotics (SGAs)

Similarly to FGAs, SGAs have their mode of action on D2 receptor antagonists as well as 5-HT2A (Serotonin) receptors. SGAs have a higher affinity for 5-HT2A (Serotonin) receptors than D2 receptors, thereby exhibiting fewer extrapyramidal side effects. However, compared with FGAs, SGAs’ have a higher risk of metabolic side effects leading to metabolic syndrome. This can lead to increased risk of HTN, diabetes and cardiovascular complications.

Source: Adapted from: National Health Service. Metabolic syndrome [internet]. 2019 [cited 2022 July 15]. Available from: https://www.nhs.uk/conditions/metabolic-syndrome/

Source: Adapted from: National Institute for Health and Care Excellence. Psychoses and related disorders [internet]. [cited 2022 July 15]. Available from: https://bnf.nice.org.uk/treatment-summaries/psychoses-and-related-disorders/

Clozapine 

Indication

Clozapine is an atypical antipsychotic that is reserved for use in treatment-resistant schizophrenia. It has also been shown to be efficacious against negative schizophrenic symptoms, suicidal and self-harm symptoms. Other indications for clozapine include intolerance to typical or atypical antipsychotics due to extrapyramidal side effects or tardive dyskinesia.

Clozapine drug monitoring

Clozapine is an expensive medication to prescribe, partly due to the fact that it requires intense monitoring via regular blood tests, physical health monitoring and strict regulation on dispensing. The diligent supervision of Clozapine is due to the potentially fatal risk of agranulocytosis. Prior to initiation, the individual must have an FBC to rule out pre-existing haematological disorders (particularly neutropenia). This is then followed by weekly blood tests for 18 weeks, then fortnightly for up to one year. Once stabilised, the frequency of blood tests is reduced to monthly.

Blood test results are reported using a traffic light system.

Green: WBC>3.5, Neutrophils >2.0

Amber: WBC 3.0-3.5, Neutrophils 1.5-2.0

Red: WBC <3.0, Neutrophils <1.5

A green result indicates that the neutrophils are within range, so the patient can continue to take their medication as normal. An amber result should be acted upon with increased blood test monitoring (twice weekly). The clinician (Consultant Psychiatrist) will need to assess the situation and investigate any causative factors that may have contributed to this result, such as concomitant immunosuppressive treatment for another condition, before making a decision regarding a reduction in the treatment dose. If a Red result occurs, then Clozapine will need to be stopped IMMEDIATELY. The patient’s blood counts are low enough to significantly increase their risk of infection and sepsis. Restarting Clozapine following a red result is not straightforward, even if subsequent green results have been obtained. A multidisciplinary team will need to be involved in this decision-making process, weighing up the risks and benefits for each individual patient. It may require re-trialling other antipsychotics before testing it once more.

References

• UpToDate. Guidance for prescribing clozapine in schizophrenia [internet]. 2022 [cited July 15]. Available from:: https://www.uptodate.com/contents/guidelines-for-prescribing-clozapine-in-schizophrenia?search=clozapine&source=search_result&selectedTitle=2~112&usage_type=default&display_rank=1
• Clozaril Connect. Clozaril, neutropenia and agranulocytosis, red alert management [internet]. 2018 [cited 2022 July 16]. Available from: https://www.hcpinfo.clozaril.co.uk/-/media/clozarilcouk/pdf/factsheet-red-alert-management.pdf

Prognosis

There is currently no singular cure known to treat schizophrenia; with complete resolution being relatively uncommon. A small proportion of patients may have only a singular episode throughout their lifetime, whereas others will have either recurrent episodes or continuous symptoms. A few factors are known to influence the longitudinal trajectory of the illness and can be used to somewhat predict how an individual will be affected. Factors such as prominent negative symptoms are notoriously difficult to treat, as most antipsychotics have greater efficacy in treating positive symptoms than negative symptoms. Of course, this will be different for each patient individually, but it is worth bearing these prognostic factors in mind so they can be addressed in a patient’s treatment plan, when feasible.

Source: Adapted from:  Saddock J, Saddock V. Concise textbook of clinical psychiatry. 3rd ed. Philadelphia: Wolters Kluwer; 2008.