What Should We Know About Treatment Of Schizophrenia

The field of abnormal psychology explores a multitude of mental illnesses like bipolar disorder, borderline personality disorder, depression, post-traumatic stress disorder and so on. The goal of abnormal psychology is to gain insight on the disorder presented, to aid clinicians in understanding what disorder to diagnose, the cause of the disorder, and prognosis for the individual. Embracing this field, we will examine schizophrenia. Schizophrenia is a mental illness which is frequently overlooked and overshadowed by more prevalent illnesses such as depression or anxiety disorders. For example, did you know that individuals with schizophrenia have a life span that is 25 years shorter than other members of the general population? (Advokat, Comaty & Julien, 2014). In this paper, we will examine the symptoms and characteristics of schizophrenia, the cause of the disorder, and treatment options, as well as some effective medications commonly prescribed and finally future research in this area.

Background and Possible Cause

Schizophrenia is a chronic mental disorder affecting 1% of the population (Advokat, Comaty & Julien, 2014). This mental illness is categorized as a neurodevelopmental disease due to the fact it is heavily correlated with brain abnormalities within the structure; which in turn impact the normal functioning of the brain and causes symptoms of psychosis like hallucinations, thought disorder and delusions (Butcher, Hooley & Mineka, 2014). These symptoms of schizophrenia are often referred to as positive symptoms because they are frequently seen in those suffering from psychosis. Further symptoms that accompany this illness are issues like social withdrawal, loss of motivation and interest, as well as a flat effect on emotions (in respects to expression and reaction). These symptoms are known as negative symptoms because they disrupt what are viewed as normal behaviors and emotional processes. These negative symptoms of schizophrenia are responsible for the poor or disabled functioning that occurs with this disorder. Symptoms of schizophrenia often being to manifest in the teen and young adult years, with most being diagnosed as sufferers’ move into adulthood, but the onset of schizophrenia can occur between the ages of 15 and 45 years old (Reinstein et al., 2002).

Currently, the direct cause of schizophrenia has not been discovered but researchers have linked schizophrenia heavily to genetic factors. If schizophrenia runs in a family bloodline, all members of that bloodline are at risk for developing schizophrenia, but those with a closer blood relationship (i.e. a mother with the disorder who has children,) have greater risk for developing this disorder than more distant relatives (Butcher, Hooley & Mineka, 2014). Currently it is thought that an abundance of genes, all having a small affect but ultimately in conjunction, contribute to the development of schizophrenia (Butcher, Hooley & Mineka, 2014). Genes currently linked in relation to schizophrenia include multiple dopamine receptor genes, the COMT (Catechol-O-methyltransferase) gene, the dysbindin gene, the DISC1 (“disrupted in schizophrenia”) gene and the C4 (complement component 4) gene (Butcher, Hooley & Mineka, 2014; Sekar et. al., 2016).

Although there has been no specific or direct cause identified yet, there are treatment options available for those suffering with schizophrenia. Schizophrenia has come a long way in the last 75 years regarding treatment. There are a multitude of options for treatment; including medications, different therapies and sometimes a combination of treatment options depending on the severity of the case. We will start by examining several types of therapies that aid those suffering in managing this mental illness; some therapies include: cognitive behavioral therapy (CBT), cognitive remediation, individual psychotherapy and family therapy treatment. These psychosocial treatments will be discussed first and later we will move on to pharmaceuticals that treat schizophrenia.

Therapeutic Treatments

Cognitive behavioral therapy is a psychosocial therapy used for a variety of mental illnesses including schizophrenia, and is said to be one of the most effective therapeutic treatments for this disorder along with many others. The premise of this therapy is to gain insight of the patient’s thoughts and feelings which contribute to negative behaviors, which aids in the reduction of positive symptoms and reduce social disability as well. CBT can help clinicians and patients to work together to find patterns of unhealthy thoughts which contribute to some of their behaviors. Cognitive behavioral therapy is credited for being an effective treatment in giving schizophrenia sufferers the tools necessary to manage some of their symptoms through skill techniques taught, which in turn help the patient be able to function. By being able to identify the correlation between thoughts and behaviors, the practitioner can begin to work with the sufferer in developing more constructive ways of thinking and healthier behaviors (National Institute of Mental Health, n.d.). For example, if they learn what situations stimulate or trigger hallucinations, they can work with the therapist to develop coping mechanisms and how to prevent these triggers.

A study by Izabela Nowak, Carla Sabariego, Piotr Switaj, and Marta Anczewskadoing, conducting a systematic review focused on the extent CBT and other traditional “third wave” approaches to schizophrenia addressed symptoms as well as disabled functionality, measuring which approach was more effective from 50 studies published from January 2009 to December 2015. 35 studies focused strictly on CBT while the other 15 on the third wave approach. This review found that cognitive behavioral therapy was more effective in addressing disability related to mental function, and in turn improving mood and function (Nowak, Sabariego, Switaj and Anczewskadoing, 2016).

After cognitive behavioral therapy, there’s what’s called cognitive remediation therapy (CRT). This kind of therapy focuses more on cognitive skills like attention span, problem solving, and memory retention (Butcher, Hooley & Mineka, 2014). The driving force behind CRT is to assist patients with cognitive deficits that restrict them from living their life on a normal functioning basis, because it’s not only positive and negative symptoms that can interfere with a sufferers’ life, but cognitive impairments hinder functioning equally as much. The hope with this treatment is that by building up these cognitive impairments, it will improve self-care, job skills, and conversational skills—leading to an overall improvement in independently functioning (Butcher, Hooley & Mineka, 2014). It is suggested that cognitive remediation is used in addition to other rehabilitation strategies, as well as when the patient is deemed clinically stable (Butcher, Hooley & Mineka, 2014).

Moving on, individual or personal therapy for the treatment of schizophrenia is a practice used frequently for those suffering. This treatment approach doesn’t involve typical psychoanalytic or psychodynamic practices. Individual therapy encompasses more of a support, rehabilitation and educational approach—teaching patients different coping mechanisms and skills at various stages of their treatment, along with general education about the mental illness that may help them better understand schizophrenia (Butcher, Hooley & Mineka, 2014). Individual treatment is hard to rank in terms of effectiveness, because It depends on the severity of the schizophrenia and the level of functioning the patient is at. This doesn’t mean that individual therapy is ineffective though. In fact, patients who receive standard treatment for schizophrenia as well as individual therapy that involves psychoeducation are less likely to relapse or be readmitted to the hospital versus a patient who only seeks standard care (Butcher, 2014).

The last type of psychosocial treatment for schizophrenia we will discuss is family therapy. This type of therapy includes relatives of the sufferer and is sometimes referred to as family intervention. In family therapy or interventions, some similar procedures to individual therapy are followed like introducing the family to psychoeducation and teaching skills like communication and how to better help handle the mental illness their loved one is suffering. This is an important aid in treatment for schizophrenia patients, because having a supportive or non-supportive environment is critical to recovery. For example, in families with elevated levels of expressed emotion (which are often negative or hostile) patients have two to three times higher relapse rates than patients who live in low level expressed emotion environments and patients do better clinically (Butcher, Hooley & Mineka, 2014; Bud and Hughes, 1997). Finally, family therapy also helps with patient compliance of taking prescribed medications (Gilliam, 2002). Family therapy or intervention can contribute to the overall effectiveness of the treatment of schizophrenia.

First Generation Antipsychotic Medication

Another option for treating Schizophrenia is anti-psychotic medications, with discoveries of how specific neurotransmitters are involved in this mental illness such as dopamine, serotonin, and glutamate; science has developed a multitude of medications to help treat schizophrenia. There are what are known as first and second generation antipsychotic medications. The development of the first-generation antipsychotics was in the early 1950s, and the later development of second generation antipsychotics are primarily responsible for the progression in treatment of schizophrenia (Butcher, Hooley & Mineka, 2014). First generation medications that help treat schizophrenia include but are not limited to: Chlorpromazine, Haloperidol, Loxapine and Pimozide. These medications work and help patients with positive symptoms associated with this illness by blocking D2 receptors in dopaminergic pathways, as well as other receptors such as acetylcholine, histamine, and norepinephrine receptors (Advokat, Comaty & Julien, 2014; Butcher, Hooley & Mineka, 2014). Although first generation medications work better with reducing negative symptoms, certain side effects came along with these drugs that were severe and possibly life threatening such as Tardive Dyskinesia which causes involuntary muscle movements and other extrapyramidal symptoms; which can include neuroleptic-induced parkinsonism, dystonia, and akathisia (Advokat, Comaty & Julien, 2014). Next, we will focus more specifically on one of the first-generation antipsychotics that is still frequently prescribed to patients today.

One of the more effective antipsychotics in treating schizophrenia was introduced in the medical field in the 1952 and is known as Chlorpromazine. This medication was the first antipsychotic agent introduced to treat not only schizophrenia but other mental illnesses as well such as bipolar disorder by controlling mania episodes (Medline Plus, 2011). Chlorpromazine is a commonly prescribed due to the fact it has low potency and sedative like properties (Frankenburg, 2017). In a 2009 study conducted by Dragan B. Ravanic and colleagues measuring the effectiveness of Chlorpromazine, Haloperidol and Clozapine on schizophrenia patients over a five-year period; 325 patients suffering from chronic schizophrenia (140 women and 185 men) and found that all three medications were effective, but clozapine ranked more effective due to less adverse effects (Ravanic et al. 2009). Thus, leads to the possibility that Chlorpromazine is more effective than most second-generation antipsychotics except Clozapine. Limitations to this study include high dropout rates, as well as the fact effectiveness was based off of the safety profile of all three drugs, with Clozapine being safer.

The popularity of this drug could be based off a case by case basis, but it did show to be equally effective as Clozapine and Haloperidol in general treatment. As with all first-generation antipsychotic medications, chlorpromazine has side effects that include issues like restlessness, dry mouth, weight gain and decreased sexual drive (Medline Plus, 2011). Chlorpromazine has also shown to aid in treating some treatment resistant patients over other medications like Haloperidol; in a study of 286 treatment resistant patients, 4% were respondent to this medication (as cited Kerwin, 2007).

Second Generation Antipsychotic Medications

These severe and unpleasant side effects of the first-generation antipsychotics were the main driving factors of the development of second generation antipsychotic medications; Including medications like Clozapine, Risperidone, Quetiapine, and Aripiprazole, to name a few (Butcher, Hooley & Mineka, 2014; Advokat, Comaty & Julien, 2014). These medications work by blocking D2 receptors like first generation antipsychotics, but second generation antipsychotics can block 5HT2A receptors as well (Guzman, n.d.). Of course, not all medications are free of side effects, but these second-generation medications have seemingly less severe side effects than those of the first generation. Common side effects experienced with second generation are weight gain, diabetes and drowsiness (Butcher, Hooley & Mineka, 2014). Another possible but infrequent side effect of these anti-psychotics include sudden cardiac death (Advokat, Comaty & Julien, 2014). Although developed to be better than first generation antipsychotics, their efficacy in treating negative symptoms is not as high as researchers originally expected them to be (Möller & Czobor, 2015). We will next cover one of the second-generation antipsychotics that is said to be effective in treating schizophrenia and still prescribed to treat patients today.

This medication is known as Clozapine and was introduced around 1960 but pulled off the market in 1975 due to two epidemics in Switzerland and Finland; with patients dying from agranulocytosis (Kerwin, 2007). The condition of agranulocytosis is where not enough white blood cells are continuously produced, therefore your body cannot fight off infection. Clozapine was brought back onto the pharmaceutical market in 1989, after researchers figured out agranulocytosis is rare and can be managed (Kerwin, 2007). The reason that clozapine is so highly regarded in the treatment of schizophrenia can be attributed to a few distinct reasons. First, this medication is one of the only second generation antipsychotics to have a lower risk of extrapyramidal symptoms and it also treats both positive and negative symptoms of schizophrenia (Naheed & Green, 2001). Secondly, clozapine stands out from other medications of its generation due to the fact that it is highly effective in providing treatment for treatment resistant patients or patients who are not responding to treatment with other antipsychotics; this is critical when a minimum of 30% of schizophrenia patients are treatment resistant (Kerwin, 2007; Ojong & Allen, 2013).

In a clinical trial conducted by John Kane (1988) and associates, involving 286 treatment resistant patients (who initially did not respond to Haloperidol in the first stage of the trial) found that Clozapine was most effective in treating resistant patients in comparison to Chlorpromazine in their randomly assigned double blind study (Kane et al., 1988). 30% of patients responded to Clozapine, versus Chlorpromazine, which only had a 4% response in treatment (Kane et al., 1988; Kerwin, 2007) The third and final reason that Clozapine ranks high on efficacy is because it is effective in the reduction of suicidality and ideation. In fact, it is so effective in reducing this that the Food and Drug Administration (FDA) have approved it for the use of recurrent suicidal behavior in schizoaffective disorder and schizophrenia (Ojong and Allen, 2013). In a study conducted by Metzler and Okayli (1995), they treated 88 antipsychotic resistant patients with clozapine for periods between 6 months and 7 years; finding that only 3 patients attempted suicide (unsuccessfully) and only a few had ideation of suicide (as cited in Reinstien et. al., 2002). Similar to other second generation medications, clozapine has some unpleasant side effects such as metabolic issues including weight gain or diabetes, as well as the issue of agranulocytosis (Kerwin, 2007; Ojong and Allen, 2013). Ultimately, the benefits of this clozapine in the treatment of this disorder outweigh the possible risks and side effects this medication can have.

Future Research

As for future research and developments involving schizophrenia, researchers are attempting to find ways to manage negative symptoms and cognitive issues caused by schizophrenia because most medications only control the psychosis aspect (Advokat, Comaty & Julien, 2014). Studies are currently underway that focus on genes linked to schizophrenia. The National Institute of Mental Health published a study they co-funded, which has “pinpointed several schizophrenia-related gene variants that alter expression of other genes in illness-implicated circuitry of the human brain” (Asher, 2016). In addition to these findings, they have also, “Identified a sub-network of about 1,400 genes – including many in genomic sites linked to the illness – coding for components involved in communications between neurons that are significantly perturbed in schizophrenia” (Asher, 2016).

Another study focusing on the genetic aspect of schizophrenia was done just last year by researchers at Harvard and Broad Institute of MIT (Massachusetts Institute of Technology). In attempts to find genetic variants in the human genome that increase the risk for this mental illness, they studied 100,000 DNA samples from over 30 different countries; from this work, they found what is called a complement component 4 gene, or C4 gene (Sekar, et al., 2016). This gene is a part of our immune system and helps play a role in brain development by promoting pruning synapses during adolescence (Sekar, et al., 2016). Unlike other genes, it has a high degree of structural variability among different people, which lead to further genetic analysis of over 65,000 people, where it was then revealed that people with particular forms of the C4 gene showed higher expression of the gene; therefore, making them at higher risk for schizophrenia. So, this excessive pruning or elimination of synapses (which can happen from adolescence until late 20’s) caused by C4 genes can lead to cognitive symptoms of schizophrenia, which are often already seen during adolescents and late adulthood (Sekar, et al., 2016). Further research regarding these genes, their expression and how they interact with other biological processes could possibly reveal two things: a better understanding of the cause of schizophrenia and new treatment techniques for those suffering.

Conclusion

Various psychosocial therapies are available and continuously developing to give schizophrenia patients their life back and help get symptoms under control. Cognitive behavioral therapy is favored highly as a psychosocial therapy and arguably is more effective than other therapies. Cognitive remediation therapy is a viable treatment option for schizophrenics in conjunction with medication and other rehabilitation techniques. Personal therapy and family therapy both take focus on giving the patient and family a comprehensive understanding of psychoeducation and many tools to aid social communication along with other skills to promote independence and functionality. A prominent factor in some of these therapies is already being stabilized on medications.

Antipsychotics are an important aspect in the treatment of schizophrenia; both first and second generation medications. First generation medications have a higher risk of side effects and extrapyramidal symptoms, but medications Chlorpromazine are still used to treat some patients today. Second generation antipsychotic medications come with lower side effects but still risk of weight gain, diabetes and other metabolic issues. Clozapine is one of the more effective second generation medications with a multitude of benefits, which far outweigh any side effects or risks associated with the drug. It is important to remember that with schizophrenia, a combination of the therapies (and even medications) discussed, are needed for patients with most severe cases to be able to lead a functioning life. This can involve having psychotherapy happening accompanied by one (or sometimes more) medication(s) taken daily to manage positive and negative symptoms.

Currently research is ongoing to find the direct cause for schizophrenia, but there have been new discoveries such as the C4 gene, and how certain genes as the C4 gene play a larger role in biochemical processes and how these processes are linked to schizophrenia. With these findings and the continuation of research regarding this topic, hopefully one day the cause of this mental illness becomes clearer, so better treatment plans and drugs can be derived to help those coping with schizophrenia.

10 September 2019
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