Long term antipsychotics in the maintenance treatment of Schizophrenia

Initial Treatment

 In the treatment of individuals suffering with symptoms consistent with a diagnosis of Schizophrenia antipsychotics represent the mainstay therapeutic option. First episode symptoms of psychosis (hallucinations, delusional belief etc) are treat with antipsychotic drugs. Ideally the decision should be taken in conjunction with the service user, however in my experience the distress that people present in often means that they are unwilling, or unable, to initially discuss treatment options. Clinical guidelines from the National Institute for Health and Care excellence (NICE) state that any medication prescribed should be on an explicit trial basis – with treatment goals in terms of symptom reduction carefully documented and monitored.

The choice of antipsychotic medication is highly complex and there are a lot of options. Common choices would include, so called, Second Generation drugs – Olanzapine, Risperiodone sometimes Quetiapine. These drugs are characterised by sedative properties in addition to their indicated action and are plagued by weight gain, sexual dysfunction and metabolic disturbance in terms of side-effects. They are quite unpleasant drugs and lead to people often feeling lethargic and disconnected from reality. This last feeling is actually exactly what the drugs are doing – blocking neurotransmitters that lend emotional salience to situations and drive personal motivation. However – during a time of crisis this disconnection from reality may seem preferable to the level of distress the individual is experiencing.

 

Continued Treatment

I want to assume for the purpose of this discussion that Schizophrenia can be considered as a diagnostic condition that requires treatment with antipsychotics and psychological therapies. I am not certain this is entirely true, but for this discussion I will accept the argument.

 Let’s also assume for the purpose of this discussion that the prescribed drug does what it says on the tin and is licensed for – that is it produces a reduction in symptoms. The question arises – do you continue the antipsychotic or stop it? Both NICE and the American Psychiatric association are fairly definitive on this question – the drug should continue. When do you stop it? The guidelines don’t say, so possibly never, or, more likely when the side-effects become unbearable.

What is the evidence that continued treatment is better than pure discontinuation, or treating only during times of relapse or crisis? 

Until recently the best evidence came from a published meta-analysis by Leucht (Leucht, S., Tardy, M., Komossa, K., & Heres, S. (2012). Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. The Lancet.). This showed that in terms of symptom resolution long term treatment clearly favoured antipsychotics over placebo. But, in terms of other outcomes – Suicide, Death by any cause, death by natural cause and being in employment there was no evidence of superiority for antipsychotics.

 

Long term follow up of those on maintenance treatment

The studies included in Leucht’s meta-analysis were limited – primarily by the length of time that they followed up participants over, which makes it difficult to guide decisions about how long to continue antipsychotic treatment?

Enter a 7 year follow up study from the Netherlands (Wunderink, L., Nieboer, R. M., Wiersma, D., Sytema, S., & Nienhuis, F. J. (2013). Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy. JAMA Psychiatry, 70(9), 913). 

Wunderink and colleagues randomised participants to receive either continued maintenance treatment or directed treatment during periods of relapse. After 7 years follow up participants were interviewed again and classed as being “in recovery” if they had had 6 months of maintained symptom resolution and functional resolution. The rate of recovery in maintenance therapy was 17.6% vs 40.4% for directed therapy. 

Oh dear.

That wasn’t what was expected to happen. People on maintenance therapy were meant to be happier and experience more “recovery”. 

 

Implications

The authors are fairly conservative in their conclusions – calling for more studies to replicated their findings. Joanna Moncrieffe is less conservative – calling for change to clinical practice.

I have to say that on balance I agree with Joanna – I think this result is quite disturbing and needs an urgent review and discussion. This was a well designed study with good follow up rates and useful outcome measures. Obviously the study needs more supporting evidence, but that will be a long time coming and the findings in the short term are pretty stark.

In terms of my own clinical practice in Forensic Psychiatry unfortunately more work does need to be done as the impact of antipsychotics on violent offending and recidivism is unclear. However the incident rates of these events are very low so evidence will be hard to generalise.

In the mean time – at the least I hope this study inspires some in depth reflection and review of clinical practice.

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