3.Treatments for Schizophrenia

Schizophrenic Neurons
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Treatment plans are individualized due to the complexity of each
patient's symptoms, which parallels the complexity of the neurons affected.
Source: Schizophrenic neurons. 2011. Retrieved March 30, 2014,
from: http://www.abc.net.au/reslib/201104/r751096_6229608.bmp


Schizophrenia is a chronic and debilitating mental disorder that manifests itself in characteristic ways that include: emotional dysregulation, interrupted thought processes, delusions and paranoia.[1] Due to the prevalence of this disease in modern society, schizophrenia treatments continue to be researched in order to elucidate further methods with higher efficacy. Current treatment cornerstones reveal themselves in the different categories of pharmacological treatments and Psychosocial treatments, each with various levels of efficacy targeting specific symptoms of schizophrenia.[2] There is no single treatment method considered effective for all patients. Each treatment plan must be tailored to the specific patient, though in the Western countries, pharmacological treatments are the most commonly used for both negative and positive symptoms of psychosis. However, many of these drugs also carry long-term side effects. Psychosocial treatments are effective in social cognitive improvements, and currently many treatments undergo experimental trials as new, innovative techniques continue to emerge in the process of finding an effective treatment regime.[3]

1. Pharmacological Treatments


Treatment of Schizophrenia is challenging. There is no all-cure for this disorder; instead, most treatment programs are specialized for each patient for symptom amelioration and rehabilitation in hopes the disorder will stabilize and the patients can sustain themselves independently. Of the treatment options, pharmacological-based treatments are the most common. Factors to consider in drug-based treatments are comorbid conditions, acute and long-term consequences, past responses to treatment, and current symptoms.[4]

There have been notions of polypharmacy being an option to explore, however the usage of effective drugs such as Clozapine decrease the likelihood of being able to find a similar drug profile that could mimic its affects, without causing other effects to occur in conjunction with each other. Pharmacological treatments are meant to treat the positive and negative symptoms of schizophrenia, including the mood and hallucinatory effects. Both affect dopamine receptors as D2 receptor antagonists.[4]

Stages of Treatment
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Treatments are difficult, likely to go through various stages
of effect, relapse, and success. This visually outlines the process.
Source: Kane, J.M., & Corell, C.U. 2010.

a) First-Generation Antipsychotics (FGA)

First-Generation Antipsychotics (FGA) are known as Typical Antipsychotics, having been developed first and widely used until it was discovered that neurological adverse effects occurred as a result of usage. Haloperidol is an example of an FGA, which in increasing years have been compared to several Second-Generation Drugs and known to increase risk of such effects. These drugs are generally tested to be of lower efficacy, but because of low-cost of production, FGAs are still in the market as they are more widely available for patient needs.[4]

FGAs are categorized into high and low potency, where high potency allows for greater schizophrenic symptom relief but has many neurological side effects, including various forms of dyskinesia. Low potency is less adversely effective; however they still target muscarinic receptors (related to that of the Acetylcholine neurotransmitter needed for muscular innervation).[5]

Examples of FGAs:
* Haloperidol
* Fluphenazine
* Chlorpromazine

i. Extrapyramidal Consequences

First-Generation Antipsychotics became known to cause neurological effects, particularly those affecting the motor control system. including symptoms similar to Parkinson's Disease,tardive dyskinesia, and body rigidity. With yearly exposure, studies showed an increase of 5% in likelihood of developing such adverse neuromuscular effects. With increasing age, these extrapyramidal effects increase in incidence rate.[5]

b) Second-Generation Antipsychotics (SGA)


Known as Atypical Antipsychotics for lacking the same incidence of extrapyramidal effects as FGAs, SGAs are the antipsychotics of choice in the current market. Unfortunately, the trade-off for their high level of efficacy is the increase in metabolic effects as well as the higher cost of production.[4] These SGAs are expensive and inefficient in terms of overall production; however it is the first-line treatment against schizophrenia. It is more likely that SGAs are able to be generalized for each patient usage, as they have several drug profiles that meet the needs of patients better than that of FGAs. They reduce the positive hallucinogenic symptoms more readily than negative symptoms, such as anhedonia and depression. The lesser severity of adverse effects neurologically prompts patients to continue their treatment, with less resulting in relapse.[4][5]

Examples of SGAs:

  • Clozapine
  • Lurasidone
  • Risperidone

Many SGAs are also used for Bipolar Disorder (such as Lurasidone), Autism, and Major Depressive Disorder.[6]

i. Clozapine

Clozapine Tablets
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An example of a second-generation antipsychotic, currently with the highest efficacy rate
Source: TEVA Pharmaceuticals USA Inc. 2011. Retrieved March 30, 2014,
from: http://dailymed.nlm.nih.gov/dailymed/archives/image.cfm?archiveid=49135&type=img&name=9f67a5da-01e9-48fc-9bf0-25d9c8f8c782-12.jpg

Clozapine is a Second-Generation Antipsychotic, often suggested as a replacement for those experiencing adverse effects like tardive dyskinesia. It is the most commonly prescribed SGA, because it has tested positive in highest level of efficacy is many tests such as the CuTLASS and CATIE, two large scale efficacy tests that compared several first and second-generation antipsychotics.[4] It is known to be the most effective in refractory schizophrenia over all other current drugs, but it can also cause seizures and other severe effects.[7]

ii. Metabolic Consequences

While it is not to say that Second-Generation Antipsychotics do not also cause neurological effects such as tardive dyskinesia, but the incidence level is much decreased in comparison to First-Generation Antipsychotics.[5] Instead, SGAs are more prone to cause metabolic changes, affecting weight changes and increasing insulin resistance. SGAs also cause dyslipidemia. It has been observed that these metabolic adverse effects are seen more commonly in patients that have not taken antipsychotics before, whereas the effects were less pronounced with patients that have gone through treatment already. The blood is also affected, where an increase in salinity has increased risk of cardiovascular problems.[4]

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2. Psychosocial Treatments

“Schizophrenia cannot be understood without understanding despair.” ― R.D. Laing

Reduced psychosocial function is a characteristic of schizophrenia, reflecting impaired cognitive function. It is not difficult to imagine the difficulties not only placed upon the patient, but the supporting families and friends as well. It is with this in mind that psychosocial therapies were developed to rehabilitate social cognitive awareness and function. While not extremely widespread in schizophrenia treatment plans as pharmacological-based plans are more common, psychosocial therapy is highly recommended.

a) Evidence-Based Practices

Evidence-based practices are the therapies that have achieved sufficient success in improving the path of schizophrenia and its varying forms, through many empirical studies and randomized controlled trials (RCT). These practices can be generalized across the population of patients.[4]

i. Cognitive Behaviour Therapy (CBT)

Cognitive Behaviour Therapy is widely used instead of other counselling practices due to the effectiveness in treating social dysfunction. Specifically, it is very effective for patients experiencing both positive and negative symptoms of psychosis which adds to a high level of cortisol in the body and anxiety. CBT focuses on reduces these symptoms to allow rehabilitation and reintegration into functional society.[4] CBT specifically for psychosis (CBTp) is different from that of the typical CBT used on other disorders, as it specifies its usage on psychotic symptoms related to schizophrenia such as reducing visual and auditory hallucinations, delusions, and depression. Hallucinations also decrease in severity and duration as a result of CBTp.[8]

CBT can be conducted in both group and individual therapy, usually beginning with a bonding experience that allows the clinician to understand the experiences specific to the patient involved, while giving the proper empathy needed for the comfort of the patient, rather than challenging their belief system. [4]

ii. Training

Certain types of training are emphasized to promote individual responsibility towards their treatment plans. Commonly used training programs include Illness Self-Management Training and Social Skills Training, both are used to actively involve patients in their own recovery and incorporate functional skills for reintegration into society.[4][9] Illness Self-Management Training involves providing essential information to patients and families, education about medication adherence and the effects of non-adhering to the plan, resulting in interruptions of effectiveness. Strategies for relapse prevention are focused on in group therapy and continued individually. These 40-50 individual group sessions generally continue on for duration of 5-10 months.[4] Social Skills Training is much the same, but instead focuses on rehabilitating social skills that deteriorate as a result of schizophrenia. Patients are taught to manage stress and seek social support in groups, helping to improve capabilities in perception, social cognition, and appropriate behavioural responses. SST programs vary in length of duration, but they all include education in goal setting, positive reinforcement, and practising skills related to friendly interaction.[4]

b) Promising Practices

Psychosocial treatments not sufficiently supported through meta-analyses and individual randomized controlled trials (RCTs) are categorized under Promising Practices. These practices are those that do not meet current criteria, limited by cost or lack of empirical evidence.[4]

Some considered promising practices are:

  • Cognitive Adaptive Therapy
  • Cognitive Behavioural Therapy for PTSD
  • Medical Disease Management Interventions
  • First-Episode Psychosis Intervention
  • Helping Older People Experience Success (HOPES)
  • Supported Education and Housing
  • Prodromal Stage Intervention
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3. Experimental Treatments

a) Virtual Reality

The concept of using Virtual-Reality (VR) to facilitate new treatment options was not a new idea. In 2008, London psychologist Daniel Freeman published a paper delineating seven applications of VR usage in schizophrenic research: one of which that focuses on the development of treatments.[10] Having previous tested VR and real-life scenarios on patients with acrophobia, their level of anxiety and responses resulted in similar levels of efficacy, further underlining the ability of VR to stimulate equivalent responses to social situations as if in the real world. It became clear that this approach could be used to target deficits in social cognition left behind by the onset of schizophrenia, as the social environments could be controlled to simulate real interactions that would have normally resulted in avoidance tactics and isolation.[10]

Three usages for virtual reality as part of cognitive behavioural interventions were outlined by Freedman[10]:

  • Educating the patient of symptomatology and its associating factors that increase or decrease intensity
  • Fear-training the patient by pre-exposing them via VR to prepare them for real-life situations
  • Teaching coping strategies for symptomatology

In 2008, there were still many limitations to VR, including the knowledge that only a standardized State Social Paranoia Scale has been developed as a measure of paranoid psychosis.[10] While attempts to simulate more trials and advances into this field over the year, it wasn't until 2014 where a new pilot study was attempted to test an integrated program based in VR for bringing about improvements in social functioning in everyday life. The main idea of this pilot study was to integrate Social Skills Training (SST) into daily life, for improving self-care skills and emotion perception in a time-efficient environment because SST usually involves observing through group or individual therapy. Individual outpatients between the ages of 18-55 were the focus of the newest pilot study, with a sample size of 12.[11]

ANOVA analyses indicated there was significant progress in decreasing negative symptoms, anxiety, and improving social functioning. This VR-based intervention seems to be effective in ameliorating social dysfunction, generalizing learned skills into everyday life but the results were based on a small sample size, which indicates the need for further research.[11]

b) Hyperoxia Treatment

An innovative treatment recently investigated in the usage of oxygen (O2) in the treatment of schizophrenia. It is known that impaired mitochondrial function in converting blood sugars in the brain, as well as lower brain function in the prefrontal cortex is a result of schizophrenia. Lower oxidative phosphorylation mediated by abnormal mitochondrial activity is believed to explain the positive and negative symptomatology of schizophrenia. It was hypothesized in this study by Yehudit, B. et. al. in 2012 that by increasing O2 inside the brain, it would result in increased cognitive capacity that could reverse some of the impairments gained by the onset of disease.[3] Another study found decreased hemodynamic responses in schizophrenic patients when asked to complete specific tasks, supporting the hypothesis that deficiency in O2 results in schizophrenic symptoms.[3]

Hyperoxia therapy is already known to increase neuronal activity during traumatic events, because O2 can easily traverse in the blood and diffuse across barriers. This decreases any adverse effects from happening, as O2 is already used as an important benign resource in the body.[3] Acute therapy of cluster headaches support that hyperoxia therapy can have positive physical effects on brain function, especially when used moderately in order to reduce the probability of Reactive Oxygen Species development (ROS).[3]

In this study, 172 individuals were selected to undergo treatment but only 15 completed the full 2 months of protocol. Patients were alternated between receiving regular O2 treatment and enriched O2 inhalation treatment. Aside from a drier nose of one patient, there were no adverse physiological effects as a result of treatment. Results indicated an improvement in a PANSS scores, revealing itself behaviourally in improvements in memory and cognition when under enriched O2 inhalation treatment.[3]

Further studies need to be conducted to moderate dosage and duration to be relevant, but with this base study, it can be implied that O2 hyperoxia treatments have a place in schizophrenic treatment in the easy application and lack of adverse side effects.

Bibliography
2. Kane, J.M., & Corell, C.U. Pharmacologic Treatment of Schizophrenia. Dialogues Clin Neurosci. 12, 345-357 (2010).
3. Bloch, Y. et. al. Normobaric Hyperoxia Treatment of Schizophrenia. J Clin Psychopharmacol. 32(4), 525-530 (2012).
4. Kane, J.M., & Corell, C.U. Pharmacologic Treatment of Schizophrenia. Dialogues Clin Neurosci. 12, 345-357 (2010).
5. Leucht, S. et. al. Second-Generation Versus First-Generation Antipsychotic Drugs for Schizophrenia: A Meta-Analysis. The Lancet. 373(9657), 31-41 (2009),
6. Sanford, M. Lurasidone: In the treatment of schizophrenia. CNS Drugs. 27,: 67-80 (2013).
7. Mustafa, F.A. Schizophrenia Past Clozapine What works? J Clin Psychopharmacol. 33, 63-68 (2013).
8. Senky T., et al. A randomized controlled trial of cognitive-behavioural therapy for persistent symptoms in schizophrenia resistant to medication. Arch Gen Psychiatry. 57, 165-172 (2005).
9. Schizophrenia. Harvard Health Publications Health Topics A - Z, (04) (2011).
10. Freeman, D. Studying and Treating Schizophrenia Using Virtual Reality: A New Paradigm. Schizophrenia Bull. 34:4, 605-610 (2008).
11. Rus-Calafelt, M., Gutierrez-Maldonaldo, J., Ribas-Sabate, J. A virtual reality-integrated program for improving social skills in patients with schizophrenia: A pilot study. J Behav Ther Exp Ps. 45(1), 81-89 (2014).

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