Abstract

Antipsychotics (Aps) must be used for the duration of treatment for schizophrenia (SZ) in order to achieve remission, avoid clinical recurrence, and enhance social and personal functioning as well as quality of life in patients. The unique characteristics of schizophrenia in this age group make treating these people a substantial therapeutic challenge. Prolonged mental illness known as schizophrenia is typified by severe disruptions in thinking, feeling, and acting out. In older people Patients may experience a more complex manifestation of the illness, including a psychotic flare-up. Symptoms and cognitive deterioration that lower life quality. For many years, the dopamine hypothesis served as the only explanation for the pathophysiology of schizophrenia and was essential in the discovery of numerous conventional and atypical antipsychotics. Other than the dopamine hypothesis, the glutamate hypothesis has been the subject of the most in-depth pathophysiology research.

Keywords

Introduction

Early intervention and ongoing long-term (maintenance) treatment are necessary for the effective management of schizophrenia (SZ) in order to minimize symptoms, preserve functionality, enhance quality of life  and avoid relapse.[1] One of psychiatry’s most effective treatments for schizophrenia is antipsychotic medication.[2] A complex and long-lasting mental illness, schizophrenia is typified by a wide range of symptoms, such as delusions, hallucinations, disordered speech or behavior, and cognitive impairment. For many patients and their families, the disease is incapacitating due to its early onset and protracted course. Negative symptoms, which are defined by loss or deficits, and cognitive symptoms, which include attention, working memory, or executive function problems, are common causes of disability.[3] Chronic, recurrent, and frequently debilitating, schizophrenia is a mental illness with complex symptomology that presents as a mix of positive, negative, and/or cognitive aspects.

Antipsychotic drugs are part of the standard management of schizophrenia because they assist manage acute psychotic episodes and prevent relapses, while maintenance therapy is used long-term after patients have stabilized. Schizophrenia is treated with two primary medication classes: first- and second-generation antipsychotics (FGA and SGA).[4] Schizophrenia is a ter’Ible mental illness that affects social and mental functioning and frequently causes concomitant illnesses to arise. Both the patients’ and their friends’ and families’ lives are upended by these modifications. In addition to being able to identify early symptoms of the illness, refer patients to the right mental health professionals, assist patients and their families in coping with the devasting effects of schizophrenia, and support a multidisciplinary approach to address all aspects of the illness, family physicians can play a significant role in the effective treatment of schizophrenia.[5]

Pathophysiology –

Neurotransmission abnormalities have served as the foundation for theories regarding the pathophysiology of schizophrenia. The majority of these theories revolve around either an overabundance or a shortage of neurotransmitters, such as glutamate, serotonin, and dopamine. Other theories link the neurochemical imbalance associated with schizophrenia to aspartate, glycine, and gamma-aminobutyric acid (GABA).[6] In all civilizations, the prevalence of schizophrenia is 1%, and it affects both men and women equally.When it comes to presenting with the disease, men usually do so in their late teens or early 20s, while women often do so in their late 20s or early 30s. The biggest risk factor is a history of schizophrenia in the family. The time of year and place of birth, socioeconomic standing, and maternal infections are other potential risk factors. However, the evidence for these theories is equivocal.[7]

Etiology –

Researchers have been unable to pinpoint the exact cause of schizophrenia for over a century. However, it is generally acknowledged that a variety of factors, such as genetic predisposition and environmental effects, contribute to the illness’s varied manifestations. The possibility that schizophrenia develops as a result of brain damage sustained during pregnancy is one theory.Six obstetric problems have been linked to the development of schizophrenia in later life: bleeding during pregnancy, gestational diabetes, emergency cesarean delivery, hypoxia, and low birth weight[14].It is a major factor in the development of schizophrenia, according to the Finnish Adoptive Family Study of Schizophrenia. Additionally, it was discovered that individuals who have a genetic predisposition to schizophrenia are particularly vulnerable to the emotional climate of their family setting. A setting that is conducive to childrearing, characterized by minimal criticism and direct, unambiguous communication, seems to guard against the manifestation of this hereditary susceptibility.[15]

It was agreed upon that the following five significant elements should be include in the definition of negative symptoms.

1)Anhedonia, or the inability to experience joy;

2)Avolition (apathy)—loss of drive and enthusiasm, disinterest in routine activities;

3)Social withdrawal, characterized by disrupted social interactions and avoidance of  personal interactions;

4)Analogia—a negative cognitive disorder characterized by a reduction in speech range and a lackluster speech content;

5)A flattening or blunting of the emotions, a diminished emotional reaction to stimuli.[8]

Causes –

What causes schizophrenia is unknown. However, scientists think that a combination of environment, brain chemistry, and heredity may be involved.

Schizophrenia may be influenced by alterations in certain naturally occurring brain chemicals, such as the neurotransmitters glutamate and dopamine. Studies on neuroimaging reveal alterations in the central nervous systems and brain anatomy in individuals with schizophrenia. Although new treatments have not yet been able to be applied to schizophrenia, these findings demonstrate that the illness is a brain disorder.[9]

Diagnosis –

As previously mentioned, schizophrenia is a chronic illness characterized by a variety of symptoms, none of which are harmful on their own. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, a diagnosis of schizophrenia is made by evaluating the signs and symptoms unique to the patient (DSM-5). Delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, and negative symptoms are among the active-phase symptoms that must persist for a significant portion of at least one month in order to meet the diagnostic criteria for schizophrenia, according to the DSM-5.[10] Positive and negative symptoms that can affect a patient’s thoughts, perceptions, speech, affect, and behaviors are characteristics of schizophrenia. Hallucinations, voices conversing with or about the patient, and delusions that are frequently paranoid are examples of positive symptoms. Flattened affect, loss of pleasure, lack of will or drive, and social disengagement are examples of negative symptoms.[11]

Risk Factors –

Even though the exact cause of schizophrenia is unknown, the following seem to increase the likelihood of the disorder:

1.schizophrenia in the family history.

2.experiences in life, like being poor, stressed out, or in danger.

3.Certain problems related to pregnancy and childbirth, like inadequate nourishment before or after delivery, low birth weight, or prenatal exposure to pollutants or viruses that could impair brain development.

4.using psychoactive or psychotropic drugs, also known as mind-altering substances, when one was a teenager or young adult.[9]

Adverse Effects –

1.The Endocrine System

Up to 87% of patients receiving risperidone or paliperidone may develop hyperprolactinemia, which may result in gynecomastia, decreased libido, irregular menstruation, or sexual dysfunction.

2.Heart and Circulatory System Of patients receiving antipsychotic therapy, up to 75% may experience orthostatic hypotension.The risk seems to be highest in patients with diabetes, cardiovascular disease that already exists, or advanced age; however, all patients taking antipsychotic medications should be advised to stand up slowly from a sitting position in order to prevent a hypotensive episode.

3.Central Nervous System

Another typical adverse effect of antipsychotic drugs is dystonia. This disorder can be fatal and frequently leads to nonadherence.

4.Other Unfavorable Impacts

Other side effects that schizophrenia medications can have include the following:

It has been demonstrated that antipsychotic drugs with anticholinergic effects exacerbate narrow-angle glaucoma, so patients taking these drugs need to be closely watched. The most common side effect of chlorpromazine is opaque deposits in the lens and cornea. For patients taking quetiapine, eye exams are advised due to the possibility of cataract development.50 Patients who take thioridazine at doses higher than 800 mg per day run the risk of developing pigmentation changes in the eyes.2.

• Urinary hesitancy and retention have been linked to low-potency FGAs and clozapine. Among clozapine users, the prevalence of urinary incontinence can reach 44%, with 25% of cases being persistent.

• Risperidone and FGAs are more likely to result in sexual dysfunction [12]

5.Antipsychotic side effects can occur, and prescribers need to know when these effects are most likely to happen. Neurologic side effects are the most worrisome for first-generation antipsychotics. The development of involuntary movements linked to neurologic side effects can be tracked with the Abnormal Involuntary Movement Scale.[13]

Mechanism Of Action –

The precise mechanism of action of antipsychotic drugs is Unknown, although it has been suggested that these drugs Comprise three main categories:  typical, or traditional, Antipsychotics, which are associated with high dopamine (D2) Antagonism and low serotonin (5-HT2A) antagonism;  atypical Antipsychotics that have moderate-to-high D2 antagonism and  High 5-HT2A antagonism; and atypical antipsychotics that demonstrate low D2 antagonism and high 5-HT2A antagonism. At least 60% to 65% of D2 receptors must be occupied to Decrease the positive symptoms of schizophrenia, whereas A D2 blockade rate of 77% or more has been associated with extrapyramidal symptoms .

Method of Action Antipsychotic medications’ exact mode of action is unknown, however it has been proposed that they fall into three primary categories:

1 Conventional antipsychotics, also known as typical antipsychotics, are linked to high levels of dopamine (D2) antagonist and low levels of serotonin (5-HT2A) antagonist;

2) atypical antipsychotics, on the other hand, have moderate-to-high levels of D2 antagonist and high levels of 5-HT2A antagonist;

3) atypical antipsychotics that exhibit low levels of D2 antagonist and high levels of 5-HT2A antagonist. While extrapyramidal symptoms have been linked to a D2 blockade rate of 77% or higher, positive symptoms of schizophrenia can be reduced by occupying at least 60% to 65% of D2 receptors.[16]

Method –

The current paper was intended to be a narrative survey of the literature that included a critical analysis of the data that was at hand. Rather than doing a thorough review, our goal was to offer a reference for additional reading. As a result, no systematic literature search was made disparities in sex with Aps Disparities between the pharmacokinetics and pharmacodynamics of Aps by gender. Men and women have very different body compositions; the former have larger muscles, more adipose tissue, and smaller organs. This alters the volume of distribution, particularly for lipophilic medications like Aps. However, this difference diminishes after menopause due to the effect of female hormones on fat cells. Disparities between the sexes in treatment response and AP tolerability Women have been observed to respond to most Aps better than men, though this varies according to age. Although premenopausal women do respond better, women over  particularly those in the 65–69 age range, have a worse clinical course and may require more hospital stays. Pregnant, postpartum, breastfeeding, and postmenopausal women’s considerations Maternity. The risk of stillbirth, small/large-for-gestational-age births, preterm delivery, or spontaneous miscarriage is not substantially elevated in women who use Aps. However, information on the fetal risks of Aps is scarce and mostly based on case reports because clinical trials typically do not include pregnant participants. However, there’s a chance that the advantages of Aps exceed the risks of stopping them while pregnant.[17] The PRISMA checklist was closely adhered to during the systematic review’s methodology to guarantee openness and excellence in the choice and evaluation of the studies. Five primary criteria were used in the search, which was carried out in the PubMed, Scielo, and Web of Science databases. The objective was to locate and examine the most pertinent research on treating schizophrenia in older patients, with an emphasis on the security and effectiveness of therapeutic approaches guarantee the quality and applicability of the chosen research, inclusion criteria were established. Included were articles that discussed patients with schizophrenia who were 65 years of age or older. The chosen studies had to include unique data on the safety and effectiveness of treatments in addition to reporting particular therapeutic interventions. In order to guarantee that the data was up to date and reflected recent developments, only publications released within the previous ten years were taken into account.[18]

TREATMENT –

Non-Medical Treatment

Targeting symptoms, averting relapse, and enhancing adaptive functioning are the main objectives of treating schizophrenia in order to help the patient reintegrate into society. To maximize long-term results, both non pharmacological and pharmacological treatments must be used, as patients seldom regain their baseline level of adaptive functioning. The cornerstone of managing schizophrenia is pharmacotherapy, though lingering symptoms might still exist.

Drug Treatment

Without antipsychotic medications, it is challenging to carry out successful rehabilitation programs for the majority of schizophrenia patients. Since the majority of disease-related alterations in the brain take place within five years of the initial acute episode, it is imperative that medication treatment be started as soon as possible. Long-Acting Antipsychotic Injectable Substances

For patients who are not adhering to an oral medication regimen, long-acting injectable (LAI) antipsychotic medications present a feasible alternative. It is imperative for clinicians to ascertain whether the patient’s nonadherence can be att and Augmentative Therapy Patients who do not respond adequately to clozapine may be offered both combination therapy (using antipsychotics) and augmentation therapy (ECT or mood stabilizers).[10] ributed to unfavourable treatment outcomes. Combination.

       
           
       
Figure [21]

Outcome –

Because of the unique characteristics of this age group, choosing the right medications for the treatment of schizophrenia in elderly patients is an important decision that needs careful thought. When compared to typical antipsychotics, atypical antipsychotics often exhibit more favorable side effect profiles, making them the preferred option.It is well recognized that atypical antipsychotics, like quetiapine, olanzapine, and risperidone, are less likely to result in extrapyramidal side effects, which are especially troublesome and include tremors and muscle rigidity. When these side effects occur, patients’ mobility and general functionality may be compromised, which raises the possibility of falls and fractures. Additionally, atypical antipsychotics typically have a less severe effect on cognitive processes and the ability to focus, which is crucial for maintaining the quality of life for senior citizens who frequently experience age-related cognitive declines. Antipsychotic selection, however, should always be customized, taking into account each patient’s unique clinical circumstances as well as the existence of comorbidities. [19]

Final Veverdict –

The conclusion regarding the management of elderly patients with schizophrenia indicates that, in order to maximize clinical outcomes and quality of life, a customized therapeutic approach is necessary. Because of their more favourable side effect profiles when compared to typical antipsychotics, atypical antipsychotics are the preferred treatment option for schizophrenia in the elderly, according to scientific studies.  Drugs like risperidone, olanzapine, and quetiapine have demonstrated a decreased likelihood of extrapyramidal side effects, which are especially troublesome for elderly patients and include tremors and muscle rigidity. The decreased frequency of these effects plays a major role in maintaining overall functionality and mobility, which are important factors in lowering the risk of fractures and falls in the elderly. Antipsychotic selection should be personalized, taking into account each patient’s unique clinical circumstances as well as the existence of coexisting conditions that may make therapy more difficult. Research has indicated that continuous assessment of drug effectiveness and adverse effects is essential for modifying treatment as necessary and reducing risks.[20]

ACKNOWLEDGMENTS: The authors would like express to thankful to our Teacher Dr. Salve mam and prof. Ajit B. Tuwar for their Guidance and support for this review article. Special thanks to Sangale sir for guidance.

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