Tardive Tourette-Like Syndrome in a Patient Treated With Paliperidone

To the Editor: Tardive Tourette syndrome is characterized by the occurrence of multiple motor and vocal tics in patients on long-term neuroleptic medication; it was first reported by Klawans et al. in 1978¹ and was given its name in 1980 by Steven Stahl,² who linked it to tardive dyskinesia. Twenty-one cases have been published in the past. We report on the case of a female patient, age 22, suffering from schizophrenia, who developed a Tourette-like syndrome after treatment with paliperidone; the syndrome completely disappeared after she was switched to aripiprazole. To our knowledge, this is the first report of such side effect with paliperidone, whereas there is no such report with risperidone. Tourette's disorder was described by Gilles de la Tourette in 1885,³ and the contemporary definition includes the appearance before the age of 18 of multiple motor tics and at least one vocal tic occurring several times a day or intermittently for a minimum of 1 year, with no more than 3 consecutive tic-free months. Tardive Tourette syndrome is characterized by the occurrence of multiple motor and vocal tics in patients on long-term neuroleptic medication, and was first reported by Klawans et al. in 1978.¹ Scarce data on this syndrome exist. It is generally considered to be a rare complication of neuroleptic treatment. It was given its name in 1980 by Steven Stahl, who linked it to tardive dyskinesia.² We report on the case of a female patient, age 22, suffering from schizophrenia, who developed a Tourette-like syndrome after treatment with paliperidone. Symptoms completely disappeared after she was switched to aripiprazole. This is the 22nd case report of this syndrome in the literature.

The patient was reported to have manifested difficult behavior during adolescence, with social withdrawal and anger outbursts. At the age of 21, she manifested a significant impairment in functioning and complete social isolation. Four months later, she manifested paranoid ideation and auditory hallucinations, and she stopped eating. The first hospitalization was initiated, which lasted for 3 weeks, and she received 40 mg of ziprasidone daily without any response. When she presented to our independent practice, she was suffering from auditory hallucinations (which were giving her directions), and visual hallucinations, loosening of associations, ideas of reference and possibly control, social isolation, and severe global impairment of functioning. Her major delusion concerned accusations toward her father for raping her. She was put on paliperidone, which was titrated within 2 months to 18 mg daily because of an unsatisfactory response. At 12 mg, there was some response, but at 18 mg, the response was much better. Also, 4 mg of biperiden and 225 mg of pregabalin were prescribed because of extrapyramidal signs and anxiety, respectively. The patient disappeared for the next 4 months. One month after the initiation of 18 mg of paliperidone, she manifested galactorrhea, and 2 months after the initiation, she manifested impulsive coprolalia and verbal insults toward her father, as well as complex motor tics of the trunk and arms. Her overall behavior was described by the patient as qualitatively distinct from the rest of the psychotic experience, and she was struggling to control it. The behavior was impulsive and ego-dystonic and was not based on hallucinations or delusions, resembling the qualities of Tourette's syndrome. After the manifestation of this behavior, the patient was feeling guilt and shame. The frequency of these behaviors varied from several times every day to once daily. The patient had never experienced similar symptoms in the past. Shortly after the emergence of these symptoms, she discontinued pregabalin by herself and did not return for psychiatric evaluation for 2 more months.

In terms of symptoms, she had sustained depression accompanied by suicidal ideation, according to her, related to the idea that everything is predetermined and futile, but, otherwise, the psychotic symptoms had disappeared. The suicidal ideation and the thoughts that everything is predetermined and futile were causing much distress, and the patient was spontaneously referring to them. At this time and because of the risk of suicide, she was hospitalized for a second time for 3 weeks and put on 6 mg of risperidone and 20 mg of diazepam; however, the Tourette-like symptoms worsened; fatigue and somnolence appeared; and depression and suicidality remained unchanged. She was then put on 30 mg of aripiprazole (plus 4 mg of biperiden, which was continued), and the evaluation 2 months later revealed that she was free of psychotic and depressive symptoms and suicidality had disappeared. The Tourette-like symptoms had also disappeared completely. Complete discontinuation of diazepam led to resolution of fatigue and somnolence. The only significant side effect was mild difficulty in swallowing. Biperiden was raised to 6 mg daily, but the symptom persisted. It was then considered as being a side effect of biperiden, which causes dry mouth and increases the density of saliva (the patient had difficulty in swallowing her own saliva but not swallowing food or drinking liquids). Biperiden was gradually discontinued, and the problem disappeared. It is interesting to point out that the ideas that everything is predetermined and futile as well as the suicidal ideation also disappeared, suggesting that they might not be in the frame of schizophrenia, but, instead, were obsessive-stereotypical thinking, which constituted a medication side effect, accompanying the tardive Tourette's syndrome. It is important to note that the patient had no history of perinatal insult, head injury, childhood abnormalities (including any kind of tics, attention-deficit hyperactivity, or obsessive-compulsive symptoms), substance misuse, or medical illness. Tardive Tourette's syndrome is reported to have occurred after treatment with olanzapine,³ sulpride,⁴ haloperidol,^5–7 chlorpromazine,^1,7–9 trifluoperazine,⁷ fluphenazine,⁷ thioridazine,^8,10 mesoridazine,¹¹ perphenazine,^10,12 and combinations of neuroleptics, or after prolonged neuroleptic therapy of various types.^4,7 Therapeutically, it has been suggested that all medication should be stopped,^10,13,14 or introducing clozapine,⁵ clonazepam,^15,16 clonidine, and mesoridazine¹¹ and amisulpride.³ The current case report suggests that the syndrome also responds to aripiprazole.