Persistence of extra-pyramidal disorders and psychiatric relapse after withdrawal of long-term phenothiazine therapy.
Sixty-two chronic schizophrenics in hospital were studied. There were 32 male and 30 female patients; their mean ages were 53.6 years and 60.4 years respectively. They had all been on regular phenothiazines, principally trifluoperazine, for a mean of 9.4 years.

Placebo capsules were substituted randomly for 32 patients. Within the 16 drug-free weeks that followed, 9 (28 per cent) patients relapsed sufficiently to require reinstatement on active phenothiazines. The mean drug-free period for those 9 patients was 5 weeks. They were significantly younger, had consumed larger quantities of phenothiazines over the years, and were originally receiving larger daily doses of trifluoperazine than the 23 patients who did not relapse.

The patients were rated for the three main extra-pyramidal syndromes—motor restlessness parkinsonian rigidity and tremor and oral dyskinesia-tremor, before and after trifluoperazine was withdrawn. The mean drug-free period was 16 weeks. Comparisons were made between before and after ratings, as well as between placebo and control trifluoperazine groups. Parkinsonian rigidity and tremor, and oral-dyskinesia-tremor did not appreciably change in the placebo or control groups. Motor restlessness worsened significantly in the placebo, but not the trifluoperazine group. Of the 23 placebo patients who were without trifluoperazine for 16 weeks, 8 remained free from motor restlessness, 1 patient continued unchanged, 3 patients improved, 6 patients became worse, and 5 patients developed the disorder for the first time. There was no significant difference in any of the variables tested between the patients who deteriorated and those who remained the same or improved.

Trifluoperazine withdrawal, in this study, was therefore followed by a psychiatric relapse in 28 per cent of the patients, persistence of parkinsonian rigidity and tremor and oral dyskinesia-tremor, and worsening of motor restlessness. The implications of these findings are discussed.