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 theĀ  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

4 thoughts on “Twenty percent of schizophrenia may be treatment-resistant from onset

  1. About 30% of people with schizophrenia do not have adequate response to anti psychotic medications– funny that- i was reading somewhere the other day about a young doctor- who applied for a job in a private clinic- where they didn’t use and drugs- he said they had to sit down and talk them out of their insecurities- madness’s– turn the lights on- as opposed to off- standard in mainstream psychiatry– in the best and only way they could- with words- working in and for a facility that just didn’t use psyche drugs- he said they literally had to talk them out of their mind states- and put them on the right- mind state- positive- track-makes you wonder hey.

  2. My son Bruce was first treated with stellazine,haldol, and clozapine resulting in huge side effect issues; later many other meds, including several injectibles. He was treatment resistent causing him to withdraw from meds for periods of time. (His story is documented in my book “The Ghosts Behind Him”) In 1993 at my suggestion , he was put on a new medication called risperadol in a Nanaimo hospital. The medication together with prn thorazine resulted in a mix that ended in attempted suicide and the death of a fellow group home resident. It wasn’t until he was put on clozapine during a prolonged stint at the forensic psychiatric institute in port coquitlam that his symptom gradually subsided.

  3. I believe that psychiatry is failing with treatment of schizophrenia except those who have a partial response from clozapine. There must be more research on using different types of meds and other treatments such as optics like we use to control resistant seizures.

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