Optimal biological treatment psychosis

"Optimal biological treatment for first episode psychosis has significant differences from the treatment of more established schizophrenia." Discuss with reference to the relevant research findings.

Early treatment of first episode psychosis is of crucial importance in the improvement of the prognosis of the illness. When ensuring successful care, timely maintenance of treatment response is optimal in regards to better long term outcomes. The appropriate use of psychotherapeutic drugs to suit each individual can be a difficult task as the side effects of the medication can impact on adherence to treatment. Psycho-education in regard to illness and medication plays a major role in recovery from psychosis. The treatment of more established schizophrenia has significant differences compared to first episode psychosis. Treatment options and medications can differ as can dosages of antipsychotic medication. The emphasis is not on full recovery for chronic schizophrenia, but control of symptoms so the individual can have better quality of life.

The aim of this essay is to discuss the differences between treatment of first episode psychosis and more established schizophrenia. Antipsychotic use in regard to first generation and second generation antipsychotics will be discussed as will different treatment options for chronic schizophrenia. Strategies for maintaining adherence to treatment will also be discussed as will the reasons for non-adherence to treatment. The risk of suicide and suicide attempt will also be touched upon.

Gearing and Charach (2009) state the average age for onset of schizophrenia differs between the sexes. The average age for males is between 15 and 25 years with 39% of males having their first episode of psychosis before the age of 19 years. Twenty-three percent of females with schizophrenia have their first episode of psychosis before the age of 19 and the average onset is between 25 and 35 years (Gearing & Charach, 2009). Gearing and Charach (2009) state the primary reason for hospitalisation in psychiatric institutions is for psychotic disorders. The average length of stay for adolescents is between 25 to 45 days (Gearing & Charach, 2009).

Robinson, Bruxner, Harrigan, Bendall, Killackey, Thurley et al. (2010) state young people experiencing a first episode of psychosis experience greater negative outcomes if the psychosis has a greater duration before adequate treatment. Adolescents have had less time to develop social skills, coping strategies and general activities of daily living. The longer the psychosis goes untreated, the poorer the outcome will be in regard to their general, social and vocational functioning (Robinson, Bruxner et al., 2010)

Perkins, Gu, Boteva and Leiberman (2005) state there are at least two reasons why it is important that the causes and consequences of untreated psychosis is understood. Firstly, the period of untreated psychosis is a potentially variable prognostic aspect, and to be aware of its relation to outcome could guide the way to enhanced therapeutic strategies and public health schemes. Second, an association of period of untreated psychosis to outcome could possibly be a sign of a neurodegenerative process and so have significant implications for understanding the pathophysiology of schizophrenia. On the other hand, the duration of initially untreated psychosis could possibly be associated with the severity of illness and as a result might be a marker rather than a determinant of outcome (Perkins, Gu, Boteva, & Leiberman, 2005).

Gering and Charach (2009) report that early onset of psychotic disorders are connected with intellectual decline reflected in lowered IQ scores and reduced quality of life noticeable by a reduction in employment-related problems, daily functioning, and social deficits. Adolescent onset of psychotic disorders results in poorer outcomes than onset later in life. There has only been a limited amount of controlled studies which have investigated children and adolescents with psychotic disorders, the majority of which have found that full recovery is gained in less than 25% of younger patients (Gearing & Charach, 2009).

During the early stages of psychotic illness, the risk of suicide is at its highest. Over a four to five year follow-up the estimated rates of suicide among people with first episode psychosis is between 1 and 3% and the rate of deliberate self harm and suicide attempt are even higher at between 10% and 14% prior to presentation for treatment (Robinson, Bruxner et al., 2010; Robinson, Harris et al., 2010). The rates of suicide attempt remains high even after commencement of treatment for psychosis.

A study by McGirr, Tousignant, Routhier, Pouliot, Chawky, Margolese, et al. (2006) found that at the time of suicide, the victims were more likely to be experiencing moderate to severe psychotic symptoms than controls. It was also found that a greater severity of psychotic symptoms was a good predictor of suicide and that negative symptoms alone were did not predict suicide (McGirr et al., 2006). A meta analysis by Hawton, Houston, Haw, Sinclair and Deeks (2005) has found the poor adherence to treatment is associated with an increased risk for suicide in patients with schizophrenia (Hawton, Houston, Haw, Sinclair, & Deeks, 2005).

Perkins et al. state the severity of negative symptoms at primary treatment contact is associated with a longer period of untreated psychosis. Longer period of untreated psychosis is also connected with the response of negative symptoms to treatment.

Patients with a shorter duration of untreated psychosis have experienced greater reduction in negative symptoms in studies reviewed by Perkins et al. This may be because negative symptoms have been shown to be less responsive to anti psychotic medication than positive symptoms. The possible responsiveness of negative symptoms to antipsychotic medication may be limited after a long duration of untreated illness (Perkins et al., 2005).

Perkins et al (2005) state the possibility of relapse, even with total recovery from a first psychotic episode, is especially high. Within five years of initial treatment response, more than 90% of these patients will experience a relapse of psychotic symptoms (Perkins et al., 2005).

The major results from a meta-analysis and review by Perkins et al. found that a long-lasting episode of psychosis experienced prior to the commencement of antipsychotic treatment is linked with poorer levels of symptomatic and functional recovery from the first psychotic episode. It was also found that period of initially untreated psychosis is connected with negative symptoms severity, but not with positive symptoms severity or common psychopathology at the primary clinical evaluation (Perkins et al., 2005).

The decision on which antipsychotic drug to prescribe first for a patient with psychosis can be difficult as there are no clear recommendations that exist for this choice (Johnsen, Kroken, Wentzel-Larsen, & Jorgensen, 2010; Kumra et al., 2007) . Second generation antipsychotic drugs are usually considered first line agents for people with first episode psychosis. This is based on their ability to alleviate not only positive symptoms but also negative symptoms of schizophrenia (Abbasi et al., 2010; Johnsen et al., 2010).

The treatments of cognitive dysfunction as well as the negative symptoms of chronic schizophrenia have proven to be a huge challenge. It has been reported in several studies the use of antidepressant medication as an adjunct to antipsychotic medication to alleviate persistent negative symptoms (Abbasi et al., 2010). Negative symptoms should be a key focus in the management of chronic schizophrenia as they play an significant role and are associated to deficits in global functioning and global outcome (Abbasi et al., 2010) Joffe, Terevnikov, Joffe, Stenberg, Burkin and Tiihonen (2009) have reported the use of mirtazapine, when used in conjunction with first generation antipsychotic medication was superior to a placebo in reducing negative symptomatology in patients with chronic schizophrenia but not superior to placebo when used with second generation antipsychotic medication (Joffe et al., 2009).

Rosenheck (2008) found little or no advantage for the use of atypical antipsychotics as compared to the older typical antipsychotics, for use with patients suffering chronic schizophrenia. When atypical antipsychotic drugs were compared to typical antipsychotic drugs like intermediate-potency perphenazine or high potency antipsychotics which were used in low doses or used with prophylactic anticholinergics, there were no advantages found (Rosenheck, 2008). A randomised controlled trial conducted by Kahn, Fleischhacker, Boter, Davidson, Vergouwe, Keet, et al (2009) found that second generation antipsychotic drugs had relatively the same symptom reduction as the older first generation drugs in patients with psychotic illnesses (Kahn et al., 2009).

A recent study, as stated in Wheeler, Humberstone and Robinson (2009), found that clozapine performed better and had greater symptom reduction over one year compared to other second generation antipsychotics, in patients with chronic schizophrenia (Wheeler, Humberstone, & Robinson, 2009). Clozapine use in patients with chronic schizophrenia has been shown to decrease the length of hospitalisation and decrease the rates of relapse and need for rehospitalisation. The problematic effects of clozapine are sedation, weight gain, diabetes and the more significant side effect, Agranulocytosis. Clozapine must be used with caution, especially with the risk of partial adherence or non adherence. Patients require adequate education on the use and possible side effects of this medication (Wheeler et al., 2009). Wheeler et al. concluded that the use of clozapine was more successful than changing to another second generation antipsychotic after response failed when using a different second generation antipsychotic (Wheeler et al., 2009).

Kumra et al. (2007) state there are concerns about the severity of side effects and the lack of efficacy of first generation antipsychotics (FGAs) for use with children and adolescents with first episode psychosis. This prompted a search to find an agent which was more effective, was tolerated better and had fewer side effects, for use with younger, antipsychotic naïve, patients.

Second generation antipsychotics (SGAs) include drugs such as risperidone, olanzepine, quetiapine, ziprasidone and clozapine. These drugs, as a class, have reduced tendency to cause adverse motor side effects and prolactin increase when they are compared to FGAs of similar strength (Kumra et al., 2007). Maguire (2002) states an increase in prolactin levels can result in serious short and long term problems. Short term problems include depression, menstrual irregularities and sexual dysfunction and long term problems include osteoporosis and decreased bone density. These short term problems can be a cause of non-adherence due to the sexual dysfunction and depression. Relapse of psychosis can occur due to non-adherence (Maguire, 2002).

Kumra et al. state other factors such as impaired cognition, other side effects, and lack of insight are all associated with non-adherence among young people with psychosis. Another important determinant of patients and families' attitude toward treatment is the quality of the relationship they have with their clinicians during acute admission of first episode psychosis (Kumra et al, 2007). Non adherence to medications is being acknowledged as the "other" drug problem, as stated by Robinson, Harris, Harrigan, Henry, Farrelly, Prosser, et al. (2010). Non adherence to antipsychotic medication is associated with negative clinical outcomes and occurs in 20-56% of people with a first episode of psychosis (Cassidy, Rabinovitch, Schmitz, Joober, & Malla, 2010).

The rising costs associated with non-adherence and subsequent relapse and readmission to hospital extends into tens of billions of dollars annually (Robinson, Harris et al., 2010).

A study by Petersen, Jeppersen, Thorup, Abel, Ohlenschaeger, Christensen et al. (2005) compared integrated treatment with standard treatment to find whether there were any positive effects on clinical and social outcomes for patients with first episode psychosis.

Petersen et al. found that the integrated treatment enhanced clinical outcome and compliance to treatment. The integrated treatment was assertive community treatment. The treatment was provided by two multidisciplinary teams and included specific family involvement and social skills training. It was offered to each patient for two years. It also included psycho-educational family treatment for 18 months, in a multi family group with two therapists. This focused on problem solving and development of specific skills designed to help patients and families cope with the illness (Petersen et al., 2005).

Compliance with treatment ought to be associated with lessening in symptoms during the early phase of treatment, and as a result, symptom change offers a construct which can be used to confirm different measures of compliance (Cassidy et al., 2010).

Lee, Choi, Suh, Kim, Kim, Lee, et al. (2010) have found that second generation antipsychotic medications have advantages over typical antipsychotic medication as they have comparatively low extrapyramidal side effects but still non-adherence to medication is a big issue and Kane (2003) has suggested there is no completely reliable intervention for improving adherence to medication. Partial medication adherence or non-adherence is strongly linked to relapse of psychotic symptoms. It has been suggested (Kane, 2003; Napryeyenko et al., 2010) that the second generation medication antipsychotic, risperidone, administered by long acting injection is a well-tolerated and safe way of medication administration developed to improve adherence to psychotropic medications and help to prevent relapse in patients with chronic schizophrenia. It has been shown that patients may have fewer side effects from the depot medication than oral medication as it is released slowly into the body and therefore facilitates a lower peak plasma concentration (Kane, 2003).

The long acting injectable mediation is usually used for treating patients with chronic severe illness who are poorly compliant, but a study by Napryeyenko et al. has shown that the depot medication was also well tolerated by patients with first episode psychosis. The study consisted of 253 patients with recent onset of psychosis and ran for 6 months. The starting dose was 25mg and risperidone naïve patients had a test dose of two, 1mg oral risperidone for two days before the study began. Dosages could be increased by 12.5mg after a minimum of 6 weeks to a maximum of 50mg. Of the participants who showed a clinical response (n=201), only five relapsed. Participants showed good symptom reduction and improved quality of life. There was a high study completion rate as compared to studies using oral antipsychotic drugs (Napryeyenko et al., 2010).

As there are very few studies using long acting injectable antipsychotics in patients with first episode psychosis, further studies are warranted.

Lee at al. state there are several limitations to long acting injectable antipsychotics. As patients need to go to their doctor, hospital or community clinic for the injection, some patients fail to come in for their injections. Without the use of adequate illness education, compliance training, behaviour therapy and crisis intervention, even the most effective relapse prevention can't be expected (Lee et al., 2010)


Optimal and timely biological treatment of patients with first episode psychosis is crucial to gaining full remission from the illness. Adolescents in particular have had less time to develop skills needed for daily living such as well developed social skills and coping strategies. The longer the duration of untreated psychosis can have huge detrimental effects on their lives and the also the chance of full recovery. Second generation antipsychotics have been found to be the most effective in treating first episode psychosis because of their ability to alleviate positive symptoms as well and negative symptoms and the side effects are less severe for most people compared to first generation antipsychotics. Antipsychotic nave patients are more susceptible to side effects. Side effects play a major part in non-adherence to treatment and non-adherence to treatment increases the risk of relapse of illness. The treatment of chronic schizophrenia differs from first episode psychosis as the emphasis is on controlling symptoms, both positive and negative to a degree that the patient has a better quality of life. Valuable biological treatments for chronic schizophrenia include long acting injectable antipsychotics to assist with adherence to treatment and also the use of clozapine for treatment resistant schizophrenia. It was also found that long-acting injectable antipsychotic medication may be useful in first episode psychosis but more research is needed. Psycho-education, family involvement, compliance training and assertive community treatment all play a major role, along with psychotropic medication, in recovery and adherence to treatment.

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