Understanding Schizophrenia and Psychosis with Randall White

May 24th marks the National Schizophrenia and Psychosis Awareness Day.

On Thursday May 24th, Dr. Randall was featured on Breakfast Television in a segment to change how individuals talk and think about Schizophrenia and Psychosis.

Explaining the difference between Schizophrenia and Psychosis.

Psychosis is a generic term of a mental disorder. It occurs in several conditions, and schizophrenia is one of them, in addition to bi-polar disorder along with other brain diseases. It is a rupture with reality. People with psychosis are often paranoid with thoughts of other people trying to harm them. Other symptoms include hearing voices and as a result these individuals do not perceive the world as others typically do. They perceive the world in an augmented reality, which can be extremely scary. Also with schizophrenia, there are components of basic human function that are taken away from individuals. For example, they can lose the ability to connect with people emotionally, begin to feel withdrawn, or even lose certain cognitive abilities. These include but are not limited to the ability to plan for the future and memory function.

Highlighting common misconception about aggression for individuals with Schizophrenia and Psychosis.

There is a common misconception that people with psychosis are dangerous and aggressive or violent. While that can happen, it is actually pretty rare. People with chronic mental illness are more likely to be victims than perpetrators.

Treatment and Rehabilitation plans for patients with Schizophrenia and Psychosis and their families.

As far as treatment goes, medication is used to control the voices, scary ideas, and the anxiety. However, a patient’s recovery process is also dependent on additional factors beyond the medicinal treatment. In order for individuals to regain their basic function and ability to relate to other people, services such as counselling and cognitive remediation are crucial to aid in the recovery process. This can help with patients’ memory and problem solving skills. Another big factor is support from peers and families. Mental illnesses like Schizophrenia and Psychosis can affect entire families. It is crucial to get as much support from the whole family, if possible. As this has been shown to significantly impact the individuals healing process.

Click here for a list of helpful resources and organizations for individuals impacted by Schizophrenia and Psychosis.

What Happens to First-Episode Patients After 5 Years?

Following a first episode of psychosis, patients always want to know when they can stop taking medication. Adverse effect such as weight gain or sedation may play a role, but the need to take a daily pill or receive an injection may be inconvenient or stigmatizing no matter the side effects. Existing evidence suggests a high risk of relapse during the first 5 years if medication is discontinued, up to a 5-fold compared to continuous medication treatment, although longer-term outcomes remain uncertain. Two new studies provide further evidence about outcomes longer than 5 years.

In 2003, Drs. Eric Chen, Bill Honer and collaborators in Hong Kong initiated a randomized trial with 178 first-episode patients in several clinics. To be eligible, patients had to be free of positive symptoms during at least 12 months on medication; the mean was 21.9 months. They then received either quetiapine 400 mg daily or placebo for a year or until relapse. Following the RCT, the patients returned to the community for usual clinical care.

Ten years later, the research team followed up the 178 patients; they performed a chart review on all and interviewed 142 of them. A poor outcome was defined as death by suicide, need for clozapine treatment, or persistent positive symptoms measured by the Positive and Negative Syndrome Scale (PANSS). Of 138 patients with adequate follow-up data, 110 were taking antipsychotic medication; the mean dose was 355 chlorpromazine equivalents.

Of those subjects assigned to a year of quetiapine treatment in the RCT 10 years before follow-up, 21% had a poor outcome; of those assigned to placebo in the RCT, 39% had a poor outcome. The relative risk was 1.84 (P = 0.012). Six patients died by suicide and 11 required clozapine; the incidence of these outcomes individually did not significantly differ between the groups. The investigators also found that among subjects originally assigned to medication discontinuation, i.e. placebo, relapse of psychosis during the first 2-3 years of diagnosis seemed to mediate the elevated risk of poor outcomes.

In Finland, Dr. Jari Tiihonen and his group performed a 20-year follow up on all persons hospitalized for schizophrenia for the first time during 1972–2014. Given that everyone in Finland has health and pharmacy services recorded in a national data registry, it was possible to determine who was readmitted to hospital and who filled prescriptions for antipsychotics. Based on this data, the researchers looked at whether subjects were taking medication or had been rehospitalized at various time points and then classified them as either antipsychotic users or nonusers. I suggest readers go to the original article to gain a full understanding of the methods.

Treatment failure was defined as rehospitalization or death. The table below shows the interesting finding that patients who continued antipsychotic treatment throughout the follow-up period had the lowest risk of relapse or death, but those risks rose as a function of the duration of treatment preceding discontinuation. In other words, stopping medication after several years of stability may be more associated with poor outcome than stopping it very soon after the first episode. However, compared to those who were treated continuously, the groups that discontinued treatment at any interval had a higher rate of poor outcome.

Adjusted Hazard Ratio chart

FIGURE: Adjusted hazard ratios as a function of duration of antipsychotic use prior to discontinuation.

The number of deaths was relatively small, but available data allowed the calculation of hazard ratios in 3 matched groups: those who discontinued antipsychotic treatment within the first year, those who remained on antipsychotics throughout, and those who did not use antipsychotics.  In 3057 subjects, 91 deaths occurred; compared with continuous antipsychotic users, nonusers had a 214% higher risk of death (hazard ratio, 3.14; 95% CI, 1.29–7.68), and those who discontinued within a year had a 174% higher risk of death (hazard ratio, 2.74; 95% CI,1.09–6.89).

These studies have important limitations, given their retrospective nature and the lack of details about important outcomes related to function and comorbidities. Nonetheless, they bring new understandings to the role of antipsychotic therapy after the first few years of psychotic illness: patients who go untreated have a higher risk of remaining psychotic and of dying. But the finding that discontinuation after 5 or more years of antipsychotic therapy is highly associated with relapse suggests that stopping medication in chronic patients is risky.

References

Hui CLM, Honer WG, Lee EHM, Chang WC, et al. Long-term effects of discontinuation from antipsychotic maintenance following first-episode schizophrenia and related disorders: a 10 year follow-up of a randomised, double-blind trial. Lancet Psychiatry. 2018;5(5):432-442.

Tiihonen J, Tanskanen A, Taipale H. 20-Year nationwide follow-up study on discontinuation of antipsychotic treatment in first-episode schizophrenia. Am J Psychiatry. Published online Apr 6, 2018:

Twenty percent of schizophrenia may be treatment-resistant from onset

About 30% of people with schizophrenia do not have adequate response to antipsychotic medications other than clozapine. Treatment-resistant psychosis has no well-established predictors although early-onset psychosis and prolonged duration of untreated psychosis may be risk factors. The Genetics and Psychosis study based in South London, UK, enrolled 283 patients with schizophrenia-spectrum disorders in their first episode who underwent assessments including the Positive and Negative Syndrome Scale, Global Assessment of Functioning, and the Weschler Adult Intelligence Scale. The cohort had follow-up investigations 5 years after first assessment by means of the WHO Life Chart Schedule, intended for documenting the longitudinal course of schizophrenia.

Patients were determined to have treatment-resistant schizophrenia (TRS) if they were either treated with clozapine or failed to respond to 2 consecutive, adequate trials of non-clozapine antipsychotics. Remission of psychosis was defined as absence of overt psychotic symptoms for 6 months or more. The investigators classified the TRS as either early-onset or late-onset. Early onset TRS occurred when no remission occurred at any time whereas late-onset occurred when resistance developed after an interval of remission.

Of the original cohort, 246 or 87% had follow-up data. Four patients had died, and their mean age was significantly older than the cohort as a whole. In 33.7%, TRS had developed and their only distinguishing characteristic was a younger age of contact for treatment of psychosis: 25.2 years versus 27.9 years in the non-TRS group. Family history of psychosis, use of alcohol or cannabis, cognitive performance, and duration of untreated psychosis (DUP) did not differ between TRS and non-TRS groups. Those patients who were younger than 20 years at the time of first contact had an odds ratio of 2.49 for developing TRS, and men and Black people were also more likely to have TRS at follow-up.

About 70% of TRS patients had early-onset treatment resistance. Compared to the non-TRS group, those with early-onset TRS had a higher mean total PANSS score at baseline; 74% were male compared to 46% in the late-TRS group.

In the TRS cohort, about half the patients received clozapine, and they had on average a greater burden of total psychopathology and negative symptoms compared to the TRS patients who never received clozapine. The clozapine patients were also more likely to reside with family or friends.

According to the investigators, this is the largest first-episode cohort followed for onset of treatment resistance. They estimate that 23% of their patients had resistance to antipsychotic therapy from the onset of illness, and given the mean DUP of 4.5 weeks, which is quite brief, factors other than delayed treatment seem to be at play. If this study is generalizable, only a third of treatment resistance develops after the  onset of illness, and understanding that process could lead to prevention strategies. Furthermore, availability of biomarkers for TRS in early psychosis populations might help determine which patients would benefit from receiving clozapine immediately.

Lally J et al. Psychol Med. 2016;46(15):3231-3240. Abstract