The Cochrane Schizophrenia Group

Old side effects and old drugs; old side effects and new drugs

on April 5, 2013
silence the voices - still the visions

silence the voices – still the visions (Photo credit: Jackal1)

By Clive Adams

People using antipsychotic drugs like chlorpromazine and haloperidol get [anticholinergic] side effects such as blurred vision, dry mouth and constipation but the proportion of people experiencing these is not clear.

Past surveys are very old indeed, small and not really proper surveys at all. Their results had been perpetuated for decades without verification. They were undertaken so long ago that they were only about older drugs – so the lack of verification had resulted in bias as the older drugs held their reputation of causing these effects and the newer ones never gathered it in the same way.

The review authors took a novel approach to comparing the side effect profiles of old and new antipsychotics
Dr Mehemet Ozbilen was interested in this and came up with a good way of looking at it. He noted that Cochrane reviews have data on tens of thousands of people who have been given drugs in carefully observed situations.  He disengaged the direct comparisons and just listed the frequency of these adverse effects for everyone who has been given a specific drug in a trial – and, the number of people who had also been given that drug who could have had that adverse effect reported.

Many trials in relevant reviews reported no data on anticholinergic effects (estimate 40,000 participants) and these tended to be studies evaluating newer generation drugs. However, data were extracted from 177 studies within 54 reviews (N = 27,328 participants) making this the largest ‘virtual’ case series investigating these problems (most data are ≤12 weeks).

There seems to be no clear pattern of difference between older and newer drugs with each having their own distinct pattern of anticholinergic effects:

  • For example, for blurred vision, the newer generations of drugs have rates of between 10% and 20% e.g.
    • Risperidone, n = 1460, 6 randomized controlled trials [RCTs], 12% prevalence;
    • Olanzapine, n = 1584; 4 RCTs, 12% prevalence
  • These estimates are similar to those of the much older drugs:
    • Sulpiride (n = 186; 2 RCTs, 12%)
    • Chlorpromazine (n = 294; 10 RCTs, 11%)
  • Less than trifluoperazine (n = 167; 8 RCTs, 31%)
  • But considerably more than perphenazine (n = 410; 8 RCTs, 4%).

Newer antipsychotics do not seem to have fewer side effects than the older drugs
Under-reporting is a real problem. 40,000 people either did not see their anticholinergic effects as worth reporting, or had relevant questions asked and then did not have these reported, or were not asked if these common problems were an issue for them. In any event, blurred vision, dry mouth and constipation are important and the new drugs do not seem to give less of these problems than the old.

Ozbilen M, Adams CE, Marley J. Anticholinergic effects of oral antipsychotic drugs of typicals versus atypicals over medium- and long-term: systematic review and meta-analysis. Curr. Med. Chem. 2012;19(30):5214–8. [PubMed abstract]

Related Cochrane Reviews
Haloperidol versus chlorpromazine for schizophrenia – Leucht C, Kitzmantel M, Kane J, Leucht S, Chua WLLC (2013)
Risperidone versus other atypical antipsychotics for schizophrenia – Komossa K, Rummel-Kluge C, Schwarz S, Schmid F, Hunger H, Kissling W, Leucht S (2013)
Olanzapine for schizophrenia – Duggan L, Fenton M, Rathbone J, Dardennes R, El-Dosoky A, Indran S (2013)
Sulpiride versus placebo for schizophrenia – Omori IM, Wang J. (2012)
Trifluoperazine for schizophrenia – Marques LdO, Soares B, Silva de Lima M. (2-10)
Perphenazine for schizophrenia – Hartung B, Wada M, Laux G, Leucht S (2010)

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