Time to Flush the Meds? Cognitive Behavioural Therapy for Psychosis facilitated by Dr Andrew Amos

Journal Club Summary

Time to Flush the Meds? Cognitive Behavioural Therapy for Psychosis

26 February 2014

Facilitated by Dr Andrew Amos

Background

Schizophrenia spectrum disorders are a group of mental disorders characterised by psychotic symptoms such as delusions, hallucinations and disorganised thinking. Antipsychotic drugs are the first line of treatment for schizophrenia and have been shown to reduce relapse and mortality rates. However, many patients, consciously or unconsciously, refuse or discontinue drug treatment. Hence, the efficacy and clinical significance of this treatment has been questioned, and alternative treatment options are worth investigating.

Paper presented

Morrison et al.1 explored whether cognitive behavioural therapy (CBT) is effective for reducing psychotic symptoms in people with schizophrenia who had refused to take antipsychotic drugs. They conducted a single-blind randomized controlled pilot trial at 2 UK centres comparing the effect of CBT plus treatment as usual (TAU) with TAU alone on symptom severity and the number of adverse events in 74 patients with schizophrenia. Participants were 16-65 years old and had not been taking antipsychotic drugs for the past 6 months. They had either been diagnosed with schizophrenia or were undiagnosed but considered ultra-high risk cases who would benefit from an early intervention for psychosis. Randomisation was assigned electronically by a computerised system. Assessor and therapist were blinded but patients were aware of their treatment allocation and self-reported. Symptom severity was assessed by the total score on the positive and negative syndrome scale (PANSS), at baseline and at 3 month intervals up to 18 months. Adverse events such as death, hospital admission and attempted overdose were recorded. Analysis was by intention to treat, with an ANCOVA model adjusted for site, age, sex and baseline symptoms.

The results and author’s main conclusions were:

  • Mean PANSS scores were consistently lower in the CBT group than in the TAU group (standardised effect size of 0.46).
  • There were fewer adverse events in the CBT group than the TAU group (2 vs 8).
  • Cognitive therapy was well tolerated and drop-out rates were low.
  • CBT significantly reduces psychosis in patients with schizophrenia and seems to be a safe and acceptable alternative treatment to antipsychotic drugs.
  • A larger trial is needed.

Discussion

This study claims to be “the first randomized trial of cognitive therapy for people with schizophrenia spectrum disorders not taking antipsychotic drugs”. However, that statement is not really true because the participants of this study do not represent a general sample of schizophrenia spectrum disorders but rather a high functioning subgroup of patients with moderate baseline symptom severity and thus the best possible performance outcome. Howes et al.2 also recognises this limitation in his comment about the article in the Lancet.

Morrison et al. justify their study on the basis that antipsychotic trials do not achieve clinical significance3. This article identifies that PANSS scores less than 10 are not clinically significant but Morrison et al. do not apply this to their own research. In addition, they do not identify that most of their effect is due to general psychopathology scores, not positive/negative symptoms of schizophrenia. They have used an inappropriate total scale score rather than the psychosis specific sub scales.

Also, the authors claim that “neither group deteriorated over time, in a population that has been assumed to deteriorate without total adherence to drugs”. While this has been demonstrated for people with schizophrenia, it has not been shown to apply for this specific subgroup.

In a general population sample not taking antipsychotic drugs, the relapse rate is 64% per year. In this absolutely highest functioning group, 25% started using antipsychotics within 9-18 months, as did 25% of controls. Hence, an alternative hypothesis is that CBT only reduces distress in patients.

We also noted that the protocol was modified while the trial was ongoing to include a larger number of people. This constitutes a potential source of selection bias.

We agreed that the study has two major weaknesses. Selection trials are not generalizable and the results from this study can certainly not be extended to all schizophrenia patients, especially those with more severe forms of schizophrenia. In addition, we thought there was a measurement or interpretation problem, because a sub-clinically important difference was reported as clinically important.

Howes2 also highlights that the study had no placebo control, which could be a problem, because the placebo effect can play an important role in schizophrenia trials. In this study, it could be particularly relevant due to the nature of the intervention and the single-blinding. Further testing is thus needed and future studies should also compare CBT with antipsychotics.

Our overall conclusion for this article was that for patients with a retrospective case note/checklist diagnosis of schizophrenia spectrum disorder and most favourable prognosis, CBT may reduce distress over 9-18 months.

References:

  1. Morrison AP et al. (2014). Cognitive therapy for people with schizophrenia spectrum disorders not taking antipsychotic drugs: a single-blind randomised controlled trial. The Lancet Feb 6. http://dx.doi.org/10.1016/S0140-6736(13)62246-1
  2. Howes O. (2014) Cognitive therapy: at last an alternative to antipsychotics? The Lancet Feb 6. http://dx.doi.org/10.1016/S0140-6736(13)62569-6
  3. Lepping P, Sambhi RS, Whittington R, Lane S, Poole R. Clinical relevance of findings in trials of antipsychotics: systematic review. Br J Psychiatry 2011; 198: 341–45.

Summary provided by Michele Weber