A Critical Thinking of Antipsychotic Medication and Side Effects

Schizophrenia Patients

Divaz Hedya Putri and Julaeha

Magister Pharmacy, Faculty of Pharmacy, 17 Agustus 1945 University, Jakarta, Indonesia

Keywords: Antipsychotics, Extrapyramidal Syndrome, Metabolic Syndrome, Schizophrenia, Side Effects.

Background: Schizophrenia is the most common mental illness with a poor prognosis. Antipsychotic drugs are the main

treatment for schizophrenia, but the administration of this therapy can sometimes cause side effects that are

quite detrimental to the patient. Antipsychotic drugs are used to manage the treatment of schizophrenia. The

main goals in the treatment of schizophrenia are to reduce the frequency and severity of psychotic

exacerbations, to improve symptoms, and to improve patients' functional capacity and quality of life.

Objectives: This narrative review aims to describe the administration of antipsychotic therapy and assess the

relationship between antipsychotic therapy and the incidence of adverse events in patients with schizophrenia.

Methods: The research method used is a narrative review by searching for published articles on the

relationship between antipsychotic treatment and the incidence of extrapyramidal syndrome adverse events

in patients with schizophrenia. Results: A narrative review of 20 published journals showed that symptoms

of extrapyramidal syndrome can occur after a few days to weeks of use of typical antipsychotics. While

metabolic syndrome side effects occur after a few weeks in patients receiving atypical antipsychotics.

Conclusion: Patients on typical antipsychotic therapy experienced more extrapyramidal syndrome side effects

than patients on atypical antipsychotic therapy. However, the side effects of atypical antipsychotics were

found to be more dangerous, with a risk of death due to the metabolic syndrome side effects they caused.

1 INTRODUCTIONS

Schizophrenia is the most common mental disorder.

Mental disorders do not directly cause death, but

these disorders can make people unproductive and

dependent on others, causing prolonged suffering for

individuals, families, communities and the state.

Schizophrenia is characterised by a number of

symptoms that include significant disturbance of

reality, distortion of reality, severe personality

disorganization, and the inability of individuals to

interact with everyday life (Organization, 2022).

Schizophrenia is characterised by other more specific

symptoms, namely positive and negative symptoms.

Positive symptoms include chaotic speech, delusions,

hallucinations, and cognitive and perceptual

impairments. Negative symptoms include avolition

(decreased interest and drive), decreased desire to talk

and poor content, flat affect, and disruption of

personal relationships. People with schizophrenia

have great difficulty communicating and being

around other people. They also experience

hallucinations and illusions, so they seem to see

things that are not real (Lähteenvuo & Tiihonen,

2021).

Schizophrenia affects approximately 24 million

people worldwide, or 1 in 300 people (0.32%) (World

Health Organization, 2022). While the prevalence of

schizophrenia in Indonesia is based on data from

Riskesdas in 2013, where the prevalence of mental

disorders in Indonesia was 1.7% per 1000 population,

in 2018 it increased to 7% per 1000 population. This

is a rather drastic increase compared to 2013

(Kementrian Kesehatan RI, 2018).

Antipsychotic medications are used to treat

patients with schizophrenia. The main goals in the

treatment of schizophrenia are to reduce the

frequency and severity of psychotic exacerbations,

improve symptoms, and improve patients'

functioning and quality of life (Bahar et al., 20-21).

Antipsychotic medications are drugs that suppress

specific psychological functions without affecting

general functions such as normal thinking and

behaviour. The choice of antipsychotic medication

takes into account the predominant symptoms of

psychosis and the side effects of the medication

156

Putri, D. and Julaeha, .

A Critical Thinking of Antipsychotic Medication and Side Effects Schizophrenia Patients.

DOI: 10.5220/0012584900003821

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 4th International Seminar and Call for Paper (ISCP UTA ’45 JAKARTA 2023), pages 156-160

ISBN: 978-989-758-691-0; ISSN: 2828-853X

(Haafizah Dania, Melisa I. Barliana & Abdulah,

2019). Antipsychotic medications have a variety of

side effects and often lead to non-adherence in

patients with schizophrenia, which can negatively

affect the patient's quality of life and even cause

significant morbidity and mortality. The main side

effects of concern are the extrapyramidal syndrome

caused by typical antipsychotic therapy and the

metabolic syndrome caused by atypical antipsychotic

therapy. Symptoms of extrapyramidal syndrome side

effects or metabolic syndrome side effects may

appear several weeks after the administration of

antipsychotic medication (Sass et al., 20-23; Stroup &

Gray, 2018).

The main objective of this review of scientific

articles is to describe the pattern of antipsychotic use

and to review the incidence of antipsychotic side

effects that may occur as a result of antipsychotic

therapy during long-term treatment.

2 METHODS

The method used to write this article is a narrative

review. Unlike a systematic review, a narrative review

does not necessarily require a systematic, structured

and validated literature search method. Therefore, the

flow of article selection is not necessarily presented

(Pae, 2015). However, in this narrative review,

published articles obtained from a literature search

using the scientific research database PubMed were

used. In this narrative review, articles published up to

August 2023 and not older than 5 years are used.

Literature searches used as references in published

articles were also conducted to enrich the study.

3 RESULTS AND DISCUSSION

Schizophrenia is a chronic illness that takes a long

time to treat. People with schizophrenia can be given

different therapies. These are given in combination

over a long period of time (Doane et al, 2020; Neill et

al, 2022). Treatment for schizophrenia consists of

medication, psychotherapy and rehabilitation.

Psychosocial therapy for schizophrenia includes

family therapy, group therapy, individual therapy,

psychiatric rehabilitation, social skills training and

case management. The treatment of schizophrenia

with antipsychotics is based on the psychotic phase,

namely the acute phase with a duration of 4 to 8

weeks, followed by a stabilisation phase with a

duration of 2 to 6 months, in which symptoms begin

to decrease and there is an improvement in individual

functioning, but individuals are still likely to have a

relapse, which is then a stable phase of unlimited

duration, while in this phase positive symptoms are

minimal or absent, but negative symptoms are still

dominant (Jia et al., 2022; Saharuddin et al., 2021).

There are more male than female patients with

schizophrenia. This is because women

physiologically have the hormone estrogen, which

acts as an antidopaminergic, so it inhibits the release

of dopamine in the nucleus accumbens, and the

hormone oxytocin in women can also reduce

symptoms of psychosis by inhibiting dopamine in the

mesolimbic and improving thinking and social

perception (Handayani et al., 2017). Sex and gender

differences lead to important differences in

preferences, pharmacokinetics and kinetics (Li et al.,

2022). One study found that at the same dose of

antipsychotics (except lurasidone and quetiapine),

women had higher plasma levels than men. In

addition, the effects of antipsychotics are greater

because oestrogen increases the brain's sensitivity to

dopamine. As a result, these drugs are more likely to

be overdosed in women, and women are more likely

to have side effects from antipsychotics. This is also

because oestrogen is an important contributor to the

sex differences we see in the efficacy and tolerability

of antipsychotics (de Boer et al, 2023).

4 TYPICAL ANTIPSYCHOTIC

THERAPY

The mechanism of antipsychotics is a A drug that

inhibits dopamine D1 and D2 receptors and/or

serotonin pathways in the central nervous system and

acts on multiple receptors that can control acute

symptoms of schizophrenia, both positive and

negative symptoms. Therefore, the administration of

antipsychotic therapy to patients takes into account

the condition and the dominant symptoms

experienced by the patient. Antipsychotic drugs are

divided into two groups: first-generation

antipsychotics (APG-I), also known as typical

antipsychotics, and second-generation antipsychotics

(APG-II), also known as atypical antipsychotics.

Typical antipsychotics work by blocking dopamine

receptors, particularly in the mesolimbic dopamine

pathway, so they are often called dopamine receptor

antagonists. This means that antipsychotics are able

to reduce the hyperactivity of dopamine in the

mesolimbic pathway so that it is effective in

overcoming positive symptoms. However, these

A Critical Thinking of Antipsychotic Medication and Side Effects Schizophrenia Patients

157

antipsychotics also block dopamine receptors in the

mesocortical, nigrostriatal and tuberoinfundibular

pathways. Blocking these pathways is the reason why

typical antipsychotics often cause the side effects of

extrapyramidal syndrome and tardive dyskinesia, and

further exacerbate negative symptoms and cognitive

symptoms in schizophrenia patients (Julaeha et al,

2021).

5 ATYPICAL ANTIPSYCHOTIC

THERAPY

Atypical antipsychotics act as dopamine (D2) and

serotonin 5HT2 antagonists in the mesolimbic

pathway. Through this mode of action, atypical

antipsychotics are more effective in reducing or

eliminating both positive and negative symptoms. As

a result, risperidone is currently the first-line

treatment for patients with schizophrenia, replacing

typical antipsychotics (Saharuddin et al., 2021).

Although atypical antipsychotics are very good at

managing both positive and negative symptoms in

patients, atypical antipsychotics can also cause

extrapyramidal symptoms, but these are very rare

compared with typical antipsychotics. Side effects of

atypical antipsychotics include increased prolactin

levels, which can cause galactorrhoea and menstrual

problems in women and sexual problems in men.

Other possible side effects include constipation,

tachycardia and weight gain (Hirigo et al, 2021).

6 SIDE EFFECTS OF TYPICAL

ANTIPSYCHOTICS

Typical antipsychotics such as haloperidol and

chlorpromazine differ in the affinity with which they

bind to dopamine D2 receptors. Haloperidol is

estimated to be 50 times more potent than

chlorpromazine. Each has a different affinity for

binding to D2 receptors in the striatum, which is 70%

for chlorpromazine and 90% for haloperidol. As a

result, treatment with first-generation antipsychotics

often causes side effects in the form of extrapyramidal

syndromes that are more severe (Yulianty et al.,

2017). In addition, the anticholinergic effects that

occur with both haloperidol and chlorpromazine

monotherapy are constipation, dry mouth, blurred

vision and cognitive dullness. As a result, the addition

of anticholinergic drugs is given to schizophrenia

patients because of the side effects that affect

cognitive function in chronic schizophrenia patients

(Haddad et al., 2023).

Another common side effect of typical

antipsychotics, especially chlorpromazine, is

orthostatic hypotension. The use of antipsychotics

can increase the risk of fractures through several

mechanisms, one of which is that antipsychotics

block dopamine D2 receptors, thereby inhibiting the

effect of dopamine on the secretion of prolactin

produced in hyperprolactinemia. This can affect bone

cell metabolism and accelerate the rate of bone loss,

increasing the risk of fracture (Azimi Manavi et al,

2023).

Typical antipsychotics also have a greater sedative

effect than atypical antipsychotics, which will affect

the sleep patterns of schizophrenia patients receiving

typical antipsychotic therapy more than the sleep

patterns of schizophrenia patients receiving atypical

antipsychotic therapy (Valencia Carlo et al., 2023).

7 SIDE EFFECTS OF ATYPICAL

ANTIPSYCHOTICS

Atypical antipsychotics are the most recommended

treatment for positive and negative symptoms in

people with schizophrenia (Julaeha et al, 2020).

However, antipsychotics are quite scary when you

look at the side effects they cause, namely the risk of

sudden cardiovascular death. The risk of sudden

cardiovascular death increases in proportion to the

dose given. In addition to increasing the risk of

sudden cardiovascular death, atypical antipsychotics

also have the side effect of increasing body weight

and can increase glucose and lipid levels in the body.

Elevated glucose and lipid levels are among the

characteristics of patients at risk for adverse effects of

metabolic syndrome (Julaeha et al, 2021; Meyer &

Correll, 2023). In addition to causing adverse

metabolic effects (e.g. obesity and diabetes). One

study found that there are adverse effects of atypical

antipsychotics on adipocyte differentiation and

metabolism. This is because therapeutic

concentrations of aripiprazole or its active metabolite

dehydroaripiprazole during adipocyte differentiation

in the body interfere with glucose uptake, while fatty

acid oxidation genes increase. In addition, the

obesogenic olanzapine directly increases leptin gene

expression but does not affect adipocyte

differentiation and metabolism, potentially causing a

switch from glucose to lipid utilisation in adipocytes

in the body (Stelmach et al, 2023; Vranic et al, 2023).

Because agranulocytosis is often a serious side effect,

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clozapine should only be given to schizophrenic

patients who have not responded adequately to

antipsychotics other than clozapine. Clozapine may

also be given to schizophrenic patients who are at risk

of suicide or violence against themselves or others

(Rafizadeh et al., 20-23; Soiza et al., 2018).

8 CONCLUSIONS

Patients on typical antipsychotic therapy

experienced more extrapyramidal syndrome side

effects than patients on atypical antipsychotic

therapy. However, the side effects of atypical

antipsychotics were found to be more dangerous,

with a risk of death due to the metabolic syndrome

side effects they cause.

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