Abstract
Introduction
Case History
A 16-year-old girl was hospitalized with suicidal ideation secondary to abnormal movements, which began 5 months previously. Consultation with a movement disorder specialist was sought a month after her admission when no improvement in the movements occurred over several months of therapy.
The patient initially presented to the emergency room at 6 months previously complaining of body twitching and jerky movements of the upper and lower limbs, which were persistent in nature. She complained that the movements began in the past month and had started to worsen. She stated that she “twitched” all day until she fell asleep and that when she first awoke in the morning the “twitches are less.” Choreoathetoid movements were observed by physicians during the assessment, which involved the entire body and shifted from excessive to mild. She was discharged from the emergency room after psychiatric evaluation with a diagnosis of “possible malingering.” The patient was referred for outpatient neurological consultation, and follow-up with her community psychiatrist was recommended.
The patient consulted a neurologist after 4 months. At that time, she continued to have the movements she had at presentation to the emergency room, but felt they were worsening. She described the movements as originating in her chest and spreading to her arms. She found it impossible to suppress the movements. She found that stress, anxiety, and sleep deprivation made the movements worse. The patient reported that she was having difficulty feeding herself because of the movements. She had lost 9.5 kg since her emergency room visit. On examination, she was noted to have continuous, asymmetric, nonrhythmic, bilateral whole-body movements and jerks. The patient was unable to remain still. She weighed 41.4 kg (below the 3rd percentile). A diagnosis of psychogenic movement disorder was made, and the patient was referred back to her psychiatrist.
The patient returned to the emergency room after 1 month, complaining of anxiety and suicidal ideation. The patient stated that her abnormal movements had become unbearable and that she wanted to kill herself because of them. She was admitted to hospital with a diagnosis of conversion disorder. She was started on treatment with olanzapine and clonazepam. Her movements continued unabated throughout her hospital stay, and a second opinion on the movements was sought.
During the interview with the movement disorder specialist, the patient stated that her movements began 6 months previously and became acutely worse after 1 month, causing her to seek medical attention (her initial visit to the emergency room). She stated that the movements were not suppressible or distractible. She felt the movements worsened with any voluntary movement. The movements could be dampened by curling her trunk to the right while reclining or laying down or by clasping her hands in front of her body while walking. Only sleep resulted in complete cessation of the movements.
With respect to her medical history, the patient was diagnosed at age 14 with obsessive compulsive disorder, social anxiety disorder, and psychosis not otherwise specified. She was treated with risperidone 2.25 mg and citalopram 10 mg initially for a 3-month period. The dosages were subsequently increased to risperidone 4.5 mg and citalopram 50 mg after a suicide attempt. She remained on these medications until 1 month after her abnormal movements began, when her father stopped giving her risperidone daily and began giving her risperidone 1 mg for several days at a time whenever she complained of hearing voices. This occurred on at least a weekly basis.
On examination, the patient was noted to be cachetic and to have bruises over her extremities. She was alert, pleasant, and cooperative and able to provide a clear history. Examination revealed prominent axial/truncal dystonia causing twisting and hyperextension of the trunk and retrocollis of the head and neck. Frequent contraction of the lower face and jaw muscles were observed. The patient was unable to sit secondary to prominent hyperextension of the trunk, causing her to slip off the chair or bed. Voluntary repetitive movements of the arms caused worsening of neck and trunk dystonia and twisting movements of the other extremities. The patient obtained substantial relief of the movements by curling the trunk to the right side while reclining. With standing, the patient had prominent hyperextension of the trunk and hyperpronation of the arms, which was diminished by having the patient clasp the hands in front of her. Serial examinations revealed less prominent abnormal movements and postures on initial wakening.
Based on the history and clinical examination findings, a diagnosis of tardive dystonia was made. Olanzapine, which had been started in hospital for her psychiatric symptoms, was stopped. The patient underwent a magnetic resonance imaging under general anesthesia, testing for the DYT-1 genetic mutation, and a 24-hour urine collection for copper to rule out other causes of dystonia (such as idiopathic torsion dystonia and Wilson's disease). She was given a 1-week trial of levodopa (to rule out dopa-responsive dystonia) with no improvement. The patient was started on the anticholinergic medication trihexyphenidyl 1 mg three times a day and gradually titrated to 3 mg three times a day over a 2-week period. Within days of starting anticholinergic therapy the patient began to improve. Within 2 weeks her movements were 70% better. The patient's suicidal ideation resolved, and she was discharged home after 2 weeks. On follow-up at 2 months after starting trihexyphenidyl, the patient's dystonia was 95% resolved. Her only abnormality was found on gait examination, which revealed the absence of arm swing and a tendency to elevate the arms while walking.
Discussion
Movement disorders secondary to antipsychotic medications include (i) neuroleptic induced acute dystonia, (ii) neuroleptic induced acute akathisia, (iii) neuroleptic induced parkinsonism, and (iv) neuroleptic induced tardive dyskinesia (American Psychiatric Association 2000). Neuroleptic induced acute dystonia is an acute dystonic reaction that occurs within days of starting an antipsychotic medication or raising the dose. Neuroleptic induced acute akathisia (feelings of restlessness accompanied by fidgety movements and inability to remain still) and parkinsonism (tremor, rigidity, akinesia) begin within weeks of starting an antipsychotic medication or raising the dose. Tardive dyskinesia occurs with longer exposure to antipsychotics, with the Diagnostic and Statistical Manual specifying a minimum duration of 3 months (1 month if age over 60 years). Symptoms may also begin on withdrawal of neuroleptic medications. Tardive dystonia is considered a distinct subtype of tardive dyskinesia, with unique clinical manifestations and therapy. The term tardive dystonia is used to describe sustained, slow, involuntary twisting movements affecting the limbs, trunk, neck, or face, associated with neuroleptic therapy. This is distinct from classic tardive dyskinesia, a term usually employed to describe oral choreiform/stereotypic movements in association with neuroleptic therapy. Tardive dystonia can be generalized, segmental, or focal. Common manifestations include retrocollis, facial grimacing affecting the lower face, opisthotonic trunk extension, and hyperpronation of the arms. In the largest described case series (Burke et al. 1982), the average duration of exposure to antipsychotic medications prior to onset of tardive dystonia was 3.7 years (range: 3 days to 20 years). Of the 42 cases described, 8 were 18 years of age or younger at the time of onset of tardive dystonia symptoms. Younger individuals were more likely to have generalized dystonia.
This adolescent developed signs and symptoms of tardive dystonia at 2 years after the initiation of risperidone treatment for symptoms of obsessive compulsive disorder (OCD), social anxiety disorder, and psychosis not otherwise specified. Her tardive dystonia may have been unmasked in the setting of decreasing doses of risperidone, as from 1 month after her symptom onset she began receiving the medication several times per week rather than on a daily basis. She displayed several classic features of tardive dystonia, including her prominent truncal dystonia and opisthotonus, retrocollis, lower facial contractions, and hyperpronation of the arms. She also had two sensory tricks to diminish her dystonia, a feature commonly seen also in patients with idiopathic torsion dystonia.
Over time, the notion that second-generation antipsychotics (SGAs) are associated with a lower risk of neurological side effects than first-generation antipsychotics has been called into question, leading to more in-depth analysis of clinical trial data. Miller et al. (2008) performed an analysis of data from the CATIE schizophrenia trial to rigorously assess and compare the incidence of treatment-emergent parkinsonism, dystonia, akathisia, and tardive dyskinesia associated with SGAs and perphenazine in adults. Analysis revealed that there were no significant differences in the incidence or change in rating scales for parkinsonism, dystonia, akathisia, or tardive dyskinesia when comparing SGAs with perphenazine or comparing between SGAs. About 1.1%–4.5% of patients taking SGAs and 3.3% of patients taking perphenazine developed tardive dyskinesia during treatment.
Clinical trial data show that extrapyramidal symptoms are not uncommon in children taking SGA medications. In two trials of risperidone in adolescents with schizophrenia, 10 of 19 patients in one trial (Sikich et al. 2004) (mean dose: 4 mg/day) and 14 of 41 patients in the second trial (Sikich et al. 2008) (mean dose: 2.8 mg/day) required anticholinergic therapy for extrapyramidal side effects of treatment. Correll and Kane (2007) performed a systematic review looking specifically at 1 year incidence rates of tardive dyskinesia in children treated with SGAs. An analysis of 10 nonrandomized studies lasting at least 11 months and reporting on new cases of tardive dyskinesia was performed. Seven hundred eighty-three children were included, 737 treated with risperidone (mean dose: 1.58 mg/day), 27 treated with quetiapine (mean dose: 378.7 mg/day), and 19 treated with olanzapine (mean dose: 10.4 mg/day). Overall, three new cases of tardive dyskinesia were identified, two in children on risperidone and one in a child taking quetiapine. The relatively low rate of tardive dyskinesia in this analysis may be explained by the low medication doses used in the included studies. Wonodi et al. (2007) evaluated children receiving antipsychotic drugs for 6 months or longer for tardive dyskinesia in comparison with a group of children who were antipsychotic naive. Eleven of 118 antipsychotic treated children exhibited tardive dyskinesia in comparison with none of 80 antipsychotic naive patients (p = 0.003).
Randomized, controlled trials of SGA medications in children suggest that the risk of neurological side effects is greatest with risperidone, olanzapine, and aripiprazole (Pringsheim, in press). In comparison, rates of neurological side effects with quetiapine are no different from placebo (DelBello et al. 2002, 2009; Connor et al. 2008). Neurological side effects from clozapine were not encountered in randomized trials comparing it with olanzapine (Shaw et al. 2006; Kumra et al. 2008) and haloperidol (Kumra et al. 1996). Data on neurological complications with ziprasidone in children are scarce; one placebo-controlled trial described akathisia in 1 of 16 subjects randomized to ziprasidone therapy (Sallee et al. 2000).
Treatment of tardive dystonia can be difficult. Remission of tardive dystonia is more likely with prompt discontinuation of antipsychotic therapy. Given the much greater disability associated with tardive dystonia in comparison to classic orolingual tardive dyskinesia, strong consideration should be given to discontinuation of medication. If continued antipsychotic therapy is necessary, clinicians should consider switching the antipsychotic medication to clozapine. Open-label studies and case reports have shown that this may ameliorate dystonia (Friedman 1994; Adityanjee and Esterera 1996; Bassitt and Neto 1998). With respect to pediatric data, there is a case report of tardive dystonia in an adolescent associated with thioridazine treatment, which was successfully relieved with clozapine therapy (Conus et al. 2002).
If antipsychotic medications can be stopped, clinicians should taper the medication over a few weeks and treat the dystonia with an anticholinergic medication such as trihexyphenidyl. Anticholinergic medications are commonly used by movement disorder specialists for the treatment of dystonic disorders. There is a single case report of an adolescent with tardive dystonia associated with pimozide and thioridazine treatment, which was successfully relieved with benztropine therapy (Monteiro 1985).
If there is an inadequate response to anticholinergic medication, the clinician can consider botulinum toxin injections for focal dystonia (e.g., refractory cervical dystonia and lingual dystonia) (Chatterjee et al. 1997), tetrabenazine (Jankovic and Beach 1997), or baclofen (Rosse et al. 1986). Consultation with a neurologist specializing in movement disorders should be considered. Intrathecal baclofen (Dressler et al. 1997) can be used for refractory tardive axial dystonia. Several case reports suggest that bilateral pallidal deep brain stimulation is effective for severe treatment-refractory tardive dystonia (Franzini et al. 2005).
In summary, tardive dystonia can occur in children treated with SGA medications. Clinicians should have a high degree of suspicion for a neuroleptic induced movement disorder in any child developing abnormal movements while taking antipsychotic medications. As this case demonstrates, the diagnosis of psychogenic and drug-induced movement disorders can be challenging, and the costs of misdiagnosis can be very high. Consultation with a movement disorder specialist may be helpful.
Disclosure
Tamara Pringsheim has no conflicts of interest to disclose.