Effect of intravenous injection of biperiden and clonazepam in dystonia

The acute effect of intravenous injections of biperiden and clonazepam was investigated in 14 patients with various forms of dystonia (segmental dystonia, 2; generalized dystonia, 6; and Meige's syndrome, 6). Eleven patients had primary dystonia, and 3 patients had a secondary form of dystonia. Doses of 5 mg of biperiden reduced dystonia when evaluated by total scores, global scores, and subjective scores. Two patients had marked side effects in the form of dizziness. Doses of 1 mg of clonazepam significantly reduced total scores and subjective scores, but the reduction in global score was insignificant. No patient had marked side effects following injection with clonazepam. These results correspond with earlier investigations of the long-term effects of anticholinergics and benzodiazepines. It is concluded that in some cases, intravenous injections can be used as a test for evaluating both effects and side effects of antidystonic medication prior to the institution of oral treatment. Long-term intravenous treatment might be considered in individual cases.     

Pharmacological study in Meige's syndrome with predominant blepharospasm

Objective quantification of the symptoms of Meige's syndrome is difficult and has not been performed in the majority of pharmacological studies of Meige's syndrome published so far. The aim of the present study was to reexamine the therapeutic potential of biperiden, clonazepam, haloperidol, and lisuride using an objective method of quantification of the symptoms. Eleven patients received daily i.v. injections of biperiden, 5.0 mg; clonazepam, 1.0 mg; haloperidol, 2.5 mg; lisuride, 0.05 mg; and placebo in randomized order. The symptoms of the patients [idiopathic blepharospasm (IB), in 11 patients, oromandibular dystonia (OMD) in four patients] were quantified by a blind observer counting the frequencies and recording the cumulative duration of sustained spasms of IB and OMD over periods of 4 min before, and 15, 30, 60, 90, and 120 min after the i.v. challenges. Baseline quantification of IB and OMD was performed at identical intervals on randomized days of the trial. Significant improvement of the IB scores was found in response to biperiden and clonazepam and a trend toward improvement in response to lisuride (Wilcoxon test). Evaluation of the individual IB scores of each patient following the various drug challenges failed to predict the therapeutic potential of these drugs for subsequent oral treatment.     

Neuroleptic-associated tardive syndromes

We have briefly reviewed the literature on late-onset akathisia, dystonia, and Tourette-like syndrome in patients on long-term neuroleptic treatment. To date, there is no satisfactory epidemiologic or other evidence directly implicating neuroleptics in the etiology of these so-called tardive syndromes. Similarities between these disorders and tardive dyskinesia, however, make them worthy of some consideration.     

Neuroleptic-induced Tardive Tourette treated with clonazepam: a case report and literature review

Tardive Tourette syndrome has been reported as a rare complication of neuroleptic treatment. This report describes the first case of neuroleptic-induced tardive Tourette syndrome in the Latin Americas and supports the successful treatment of this disorder with clonazepam. The syndrome developed in a female schizophrenic patient who discontinued medication after 8 years of continuous neuroleptic therapy. Symptoms were unresponsive to increased doses of typical antipsychotics and treatment with an atypical antipsychotic. Significant, sustained improvement occurred with clonazepam. In this report all cases of adult-onset tardive Tourette are reviewed.     

Effects of propranolol in tourette syndrome

Alternate medications for the treatment of Tourette syndrome are required because haloperidol in some patients either may be ineffective or may cause disturbing side effects. Propranolol, a beta-adrenergic blocking agent, has been reported as effective, in uncontrolled trials, in ameliorating symptoms of tic disorder, tardive dyskinesia, and drug-induced extrapyramidal syndrome. Propranolol, in doses up to 120 mg per day, was administered to five patients with Tourette syndrome in a placebo-controlled study and was found ineffective in ameliorating symptoms of Tourette syndrome. Results underscored the importance of placebo-controlled investigation when evaluating the effects of drugs in Tourette syndrome.     

Oromandibular dystonia associated with fluoxetine

A 66 year old patient with major depression treated with fluoxetine developed persistent oromandibular dystonia and mild akathisia. She improved significantly after discontinuation of the drug and treatment with biperiden. The temporal relationship between the use of fluoxetine and the occurrence of dystonia and akathisia suggests that fluoxetine may have induced tardive dystonia in this patient possibly due to a serotonergically mediated inhibition of striatal dopaminergic neurotransmission. We believe that this is the first reported case of persistent or tardive dystonia associated with fluoxetine treatment     

Tardive dystonia provoked by concomitantly administered risperidone

Two cases of tardive dystonia are reported. The first case was an 18-year-old schizophrenic woman suffering from parkinsonism and hypotension induced by antipsychotic drugs. Risperidone (4 mg/day) was added to her drug regimen and after increasing the dosage to 6 mg/day, she began to exhibit retrocollis. The second case was a 61-year-old woman who had schizophrenia and tardive dyskinesia. After replacing chlorpromazine (75 mg/day) with risperidone (4 mg/day), she began to exhibit retrocollis. The retrocollis in both cases was considered to be tardive dystonia provoked by risperidone administered concomitantly with other antipsychotics. Risperidone is reported to produce few extrapyramidal symptoms, but these cases suggested that changing from other drugs to risperidone, or rapidly increasing risperidone dosage, may provoke tardive syndrome.     

Ziprasidone-induced tardive laryngeal dystonia: a case report

Tardive laryngeal dystonia, a rare form of dystonic syndrome, was only reported to be induced by typical antipsychotics. Here, we report one case of ziprasidone-induced tardive laryngeal dystonia in a schizophrenic female patient, who showed dysphonia, hoarseness and dyspnea after taking ziprasidone 120 mg/day for 8 months. These symptoms were significantly improved after discontinuing ziprasidone and increasing the dose of trihexyphenidyl for 1 week. Although atypical antipsychotics are associated with a lower risk of extrapyramidal symptoms, caution should be taken for any tardive dystonic movement when using these medications.     

Biperiden for treatment of somnambulism in adolescents and adults with or without epilepsy: Clinical observations

BackgroundSleepwalking in adolescents and adults may lead to serious injuries and require treatment. Anecdotal treatment recommendations include benzodiazepines (which also work in focal seizures of the frontal lobe that are an important differential diagnosis), imipramine and amitriptyline.MethodsWe assessed in a follow-up study of 4 years (medium, range: 2–7 years) the usefulness of the antiparkinsonian drug biperiden (Akineton©), an acetylcholine antagonist with high affinity for muscarinic M1-type receptors, in four consecutive cases of arousal disorder with sleepwalking and confusional behavior in adolescents and adults with or without epilepsy who did not respond to diazepam, clonazepam or amitriptyline.FindingsThe adjunctive use of biperiden was associated with reduction or remission of sleepwalking episodes in four consecutive treatment-refractory cases of arousal disorder with sleepwalking and confusional behavior. In contrast, biperiden showed no effect in a patient with REM behavioral disorder.InterpretationAlthough our observations do not and cannot establish the efficacy or safety of biperiden, it may be useful to consider biperiden for treatment of sleepwalking, if needed. A putative cholinergic mechanism of arousal disorders, including sleepwalking, provides a reasonable hypothesis why the anticholinergic agent biperiden might work. Evidence for efficacy and safety from randomized controlled trials is needed to confirm our preliminary observations.     

A case of amoxapine-induced tardive dystonia successfully treated with a low dose anti-cholinergic agent]

We report a 63-year-old man who presented with amoxapine-induced tardive dystonia. At 49 years of age, he developed depression and was administrated 50 mg amoxapine, 4 mg cloxazoram and 3 mg biperiden per day. The daily dose of amoxapine was gradually increased up to 150 mg at 58 years of age. At 61 years of age and after having been taking amoxapine for twelve years, he noticed a rotating left arm and muscle pain in his left shoulder and arm while walking. At 62 years of age, he stopped taking these three drugs. However, the dystonic movements and pain both continued to get worse. Neurological findings revealed no abnormality except for a dystonic posture and movements in the neck and bilateral arms while sitting, standing and walking. Positron emission tomography with C-11 raclopride revealed a mild decrease in the dopamine D 2 receptor numbers in the bilateral striatum. However, two dopamine agonists, pergolide and bromocriptine, worsened his dystonia. In contrast, the daily administration of 2 mg of trihexyphenidyl, an anti-cholinergic agent, markedly ameliorated the dystonia symptoms. As a result, the long-term co-administration of biperiden, an anti-cholinergic agent, may mask the toxicity of amoxapine, which may induce tardive dystonia.     

Distinguishing Acute and Tardive Akathisia by Monitoring Microvibration: A Pilot Study

Abstract: One acute and one tardive akathisia patients, respectively, and 10 : neuroleptic-treated schizophrenic patients were injected with biperiden 5 : mg or saline and the response to anticholinergics was monitored by microvibration (MV) as an indicator of muscle tonus. These data were subjected to the Fast Fourier Transform and an averaged power spectrum was computed. The biperiden injection markedly reduced the power spectral values of MV in acute akathisia. In contrast with acute akathisia, the biperiden injection sigdlcantly increased the power spectral values of MV in tardive akathisia. The subjective feelings of akathisia patients were parallel to the power spectral values of MV. Control patients were not aflected by such treatment. The present findings show that the subjective symptoms of akathisia can be well defined by the objective, differential response to anticholinergics in a manner similar to the visible extrapyramidal symptoms (dystonia, dyskinesia) induced by neuroleptics.     

Duloxetine-related tardive dystonia and tardive dyskinesia: a case report

Tardive dyskinesia and tardive dystonia are caused by dopamine receptor blocking agents, mostly antipsychotics and sometimes antidepressants or calcium channel blockers. Duloxetine-related tardive syndrome is rarely reported in the literature. We report one case of tardive dystonia and tardive dyskinesia occurring in a 58-year-old female with major depressive disorder, who developed distressing oral dyskinesia, mandibular dystonia with trismus and dystonia over left neck after treatment of duloxetine (30–60 mg per day) for 18 months. Despite discontinuation of duloxetine, she only obtained partial remission. Even though this association has been rarely reported, duloxetine may pose a potential risk of inducing tardive syndrome. Clinicians should cautiously detect early signs of movement abnormality when prescribing antidepressants.     

Tardive dyskinesia model in the common marmoset.

Thirteen adult common marmosets (Callithrix jacchus) were given once-monthly injections of haloperidol decanoate (5-15 mg/kg i.m.) for one year. Thereafter, drug-free and treatment periods alternated at 3-month intervals. After 2.5 to 14 months, 12 monkeys showed symptoms of tardive dyskinesia (TD), such as periocular and perioral twitchings, tongue protrusions, masticatory movements, and choreic movements in arms and legs. When TD symptoms were evident, the periodic treatment was interrupted and symptoms persisted for at least 5 months after the last haloperidol dose, worsened by injection of the anticholinergic drug biperiden. An injection of nondepot haloperidol (0.12 or 0.25 mg/kg) produced a reduction of TD symptoms. At the end of the study, nondepot haloperidol was injected once a week at two doses (0.12 and 0.25 mg/kg i.m.). A syndrome of excitation with peculiar behavior, interpreted as acute dystonia, was precipitated in all animals. The animals showed sustained retrocollis, climbing upside down, biting the perch, repetitive turnings, and frequent backward movements. The dystonic movements lasted approximately 6 hours and were reduced but not completely extinguished by biperiden (0.1 mg/kg). The TD syndrome registered in marmosets may provide a useful model for screening new antipsychotics for their propensity to induce TD.     

Acquired pendular nystagmus after pontine hemorrhage]

A 60-year-old hypertensive woman had a pontine hemorrhage that caused slight right hemiplegia, deep sensory disturbance on her right side and dysarthria. Three months after the stroke, she was transferred to our hospital for rehabilitation. Approximately 6 months later, she gradually began to complain of the visual oscillation. Continual, unceasing conjugate vertical/rotatory eye movements were observed. Fixation was momentary at best because of an inability to dampen the spontaneous eye movements. Electrooculography (EOG) showed bilateral vertical/rotatory sinusoidal eye movements of 2.5 Hz frequency and 10- to 35-degree amplitude. Both vertical and horizontal optokinetic nystagmus were absent. Caloric stimulation did not evoke any responses bilaterally. There were no rhythmical movements at similar frequencies in other parts of the body such as palatal myoclonus. MRI revealed not only hematoma mainly at the dorsal pontine tegmentum but also hypertrophy of the inferior olive nucleus, suggesting disruption of the central tegmental tract. Lesions of this tract may be one cause of pendular nystagmus. Several drug therapies were investigated for the nystagmus. There was no response to baclofen 15 mg. Trihexyphenidyl 4 mg was discontinued because of drug-induced hallucinations. Tiapride 600 mg and phenobarbital 90 mg were each slightly effective in reducing both frequency and amplitude of nystagmus. Treatment with clonazepam 1 mg resulted in the striking disappearance of nystagmus. She was aware of this and no longer experienced oscillopsia. Despite the visual benefit, however, the patient did not wish to continue this drug because of drowsiness and muscle relaxation. The potential long-term therapeutic application of clonazepam should be further investigated. To our knowledge, there have been no reports of successful treatment in acquired pendular nystagmus with clonazepam. Therefore, based on this favorable experience, it is suggested that clonazepam should be added to the list of potential therapies for pendular nystagmus.     

Remission of Tardive Dystonia with ECT

A 30-year-old patient with tardive dystonia, who had failed to respond to cessation of neuroleptics, placebo, diazepam, biperiden, propranolol, and clonidine, had an impressive response to courses of electroconvulsive therapy (ECT) on three successive trials.     

Multiple system atrophy with macro square wave jerks and pendular nystagmus]

A 51-year-old woman was admitted to our hospital because of gait disturbance and dysuria. Neurological examination revealed limb and truncal ataxia, orthostatic hypotension, cogwheel rigidity in all limbs, generalized hyperreflexia without pathological reflex, and horizontal gaze nystagmus. She became progressively worse and bedridden at age 52. Then she developed abnormal eye movements. Electrooculogram revealed vertical, horizontal or oblique macro square wave jerks and pendular nystagmus. Macro square wave jerks appeared during fixation and disappeared with eye closure or in the dark room. Macro square wave jerks were characterized by a duration of about 200 msec and an amplitude of 10 to 15 degrees. Pendular nystagmus with a duration of several seconds and amplitude of 5 to 15 degrees appeared when she changed her fixation or the point of fixation disappeared. Macro square wave jerks and pendular nystagmus were mildly suppressed after the intramuscular injection of 100 mg of phenobarbital, the oral intake of sodium valproate of 600 mg/day or baclofen of 60 mg/day. They were almost completely depressed after the intravenous injection of 3 mg of diazepam or the oral intake of clonazepam of 1.5 mg/day. We suggested that both macro square wave jerks and pendular nystagmus in this patient might be caused by the dysfunction of GABAergic system in the saccadic eye movement system.     

Therapeutic effect of inosine in Tourette syndrome and its possible mechanism of action

We found incidentally 3 years ago that inosine relieved the symptoms in a patient with Tourette syndrome. Since then, 36 patients suffered from Tourette syndrome were exclusively treated with inosine, 50-90 mg/kg daily in divided doses. The vocal and non-vocal tic attacks were counted either by the observation of an examiner or with a video-tape record. The clinical status was scored as the sum of the number of various tic attacks recorded during a period of 60 minutes (video-tape record) or 20 minutes (direct observation). According to the scores obtained from double blind cross-over trial (11 cases) and open trial (25 cases), the tic attacks were well controlled in 75% of patients treated. A follow-up study by the end of one year medication the efficacy of inosine was still impressive in 50% of patients. Since we have observed that inosine potentiated the release of dopamine from rat striatal synaptosomes, mimicked the action of some dopamine antagonists, it is suggested that inosine might behave as a dopamine antagonist and exerts its effect on Tourette syndrome as haloperidol does.     

Malignes neuroleptisches Syndrom durch Amisulprid

Malignant neuroleptic syndrome (MNS) is a rare side effect of antipsychotic medications but means a serious and life-threatening complication. The risk of MNS seems to be lower for second generation antipsychotics (SGA). We report the 9-month history of a 42-year-old female patient whose antipsychotic medication was switched to 800 mg per day of amisulpride. Two weeks after discharge she suffered muscular pain, stiffness, weakness of the legs, rigor, and fever. After attending our outpatient department and being diagnosed, she was transferred to the neurological intensive unit, where the creatine kinase (CK) level was measured at 160,000 U/l. Furthermore extensive rhabdomyolysis accompanied by a compartment syndrome was seen. Surgical intervention was necessary for the latter. The patient was then retransferred to the psychiatric department after treatment with lorazepam and withdrawal of antipsychotic medications. In addition a therapy with valproate sodium was conducted. Long-term high levels of CK and abnormalities in the electromyogram led to the hypothesis of myopathy as a possible risk factor, but a final diagnostic classification was not feasible. This report describes the appearance of a MNS as a consequence of SGA therapy, discusses risk factors and therapy options, and shows the 9-month course.     

Ziprasidone treatment of children and adolescents with Tourette's syndrome: a pilot study

OBJECTIVE: To evaluate the efficacy and tolerability of ziprasidone in children and adolescents with Tourette's syndrome and chronic tic disorders. METHOD: Twenty-eight patients aged 7 to 17 years were randomly assigned to ziprasidone or placebo for 56 days. Ziprasidone was initiated at a dose of 5 mg/day and flexibly titrated to a maximum of 40 mg/day. RESULTS: Ziprasidone was significantly more effective than placebo in reducing the Global Severity (p = .016) and Total Tic (p = .008) scores on the Yale Global Tic Severity Scale. Compared with placebo, ziprasidone significantly reduced tic frequencies as determined by blind videotape tic counts (p = .039). The mean (+/- SD) daily dose of ziprasidone during the last 4 weeks of the trial was 28.2 +/- 9.6 mg. Mild transient somnolence was the most common adverse event. No clinically significant effects were observed on specific ratings of extrapyramidal symptoms, akathisia, or tardive dyskinesia. CONCLUSIONS: In this limited sample, ziprasidone (5-40 mg/day) appears to be effective and well tolerated in the treatment of Tourette's syndrome. Ziprasidone may be associated with a lower risk of extrapyramidal side effects in children. However, additional studies are necessary to evaluate more fully its safety and efficacy in children with tic disorders.     

Epidemiology of tardive dyskinesia Part I.

We have performed an epidemiological study concerning tardive dyskinesia on a sample of 332 chronic schizophrenic patients (142 males and 190 females, mean age 48.6 years, mean duration of neuroleptic treatment 14.5 years). We could conclude that the age of patients at the time of assessment procedures is the most important variable. The prevalence of tardive dyskinesia was significantly higher in the older population. The significance of an insidious beginning of the illness might be only secondary to the highly significant role of the age. Other factors, such as sex, type of schizophrenia, initial syndrome, present psychic state, organic syndromes and neuroleptic-induced extrapyramidal syndrome, do not seen to play a role in the prevalence of tardive dyskinesia.