Charlotte L. Mentzel

Efficacy and safety of deep brain stimulation in patients with medication-induced tardive dyskinesia and/or dystonia: a systematic review.

BACKGROUND Tardive dyskinesia and dystonia (TDD) are severe side effects of dopamine-blocking agents, particularly antipsychotics. While deep brain stimulation (DBS) has proven effective in the treatment of TDD, little is known about the possible psychiatric complications of DBS in psychiatric patients. OBJECTIVE To assess the efficacy and safety, specifically the psychiatric side effects, of DBS in patients with medication-induced TDD. DATA SOURCES PubMed and EMBASE databases were searched systematically on May 25, 2011, for articles written in English, using the search terms deep brain stimulation AND tardive. STUDY SELECTION Of the 88 original articles retrieved, 17 studies involving 50 patients with TDD who underwent DBS were included in the review. DATA EXTRACTION Data on the severity of the movement disorders before and after DBS, as rated on the Burke-Fahn-Marsden Dystonia Rating Scale or similar scales, were extracted. Data on psychiatric symptoms before and after DBS were used to calculate the percent improvement per patient per rating scale. Overall improvement and confidence intervals were calculated using a 1-sample, 2-sided Student t test. RESULTS The mean improvement of TDD of the combined patients 3 to 76 months after implantation was 77.5% (95% CI, 71.4%-83.3%; P < .000) on the Burke-Fahn-Marsden Dystonia Rating Scale. Of the 50 patients, 1 experienced an exacerbation of depression, and 1 experienced an exacerbation of psychosis. CONCLUSIONS DBS seems to be effective and relatively safe for patients with treatment-resistant TDD; however, the results should be interpreted with caution, as most of the data are from case reports and small trials.

Effect of Antipsychotic Type and Dose Changes on Tardive Dyskinesia and Parkinsonism Severity in Patients With a Serious Mental Illness: The Curaçao Extrapyramidal Syndromes Study XII

OBJECTIVE To test the efficacy of current treatment recommendations for parkinsonism and tardive dyskinesia (TD) severity in patients with severe mental illness (SMI). METHODS We present an 18-year prospective study including all 223 patients with SMI (as defined by the 1987 US National Institute of Mental Health, which were based on DSM-III-R diagnostic criteria) receiving care from the only psychiatric hospital of the former Netherlands Antilles. Eight clinical assessments (1992-2009) focused on movement disorders and medication use. Tardive dyskinesia was measured by the Abnormal Involuntary Movement Scale and parkinsonism by the Unified Parkinsons Disease Rating Scale. Antipsychotics were classified into first-generation antipsychotic (FGA) versus second-generation antipsychotic (SGA) and high versus low dopamine 2 (D₂) affinity categories. The effect that switching has within each category on subsequent movement scores was calculated separately by using time-lagged multilevel logistic regression models. RESULTS There was a significant association between reduction in TD severity and starting/switching to an FGA (B = -3.54, P < .001) and starting/switching to a high D₂ affinity antipsychotic (B = -2.49, P < .01). Adding an SGA to existing FGA treatment was associated with reduction in TD severity (B = -2.43, P < .01). For parkinsonism, stopping antipsychotics predicted symptom reduction (B = -7.76, P < .01 in FGA/SGA-switch model; B = -7.74, P < .01 in D₂ affinity switch model), while starting a high D₂ affinity antipsychotic predicted an increase in symptoms (B = 3.29, P < .05 in D₂ affinity switch model). CONCLUSIONS The results show that switching from an FGA to an SGA does not necessarily result in a reduction of TD or parkinsonism. Only stopping all antipsychotics reduces the severity of parkinsonism, and starting an FGA or a high D₂ affinity antipsychotic may reduce the severity of TD.

Instrumental Assessment of Bradykinesia: A Comparison Between Motor Tasks

Bradykinesia, a common symptom in psychiatry, is characterized by reduced movement speed and amplitude. Monitoring for bradykinesia is important, as it has been associated with reductions in quality of life and medication compliance. Subtle forms of bradykinesia have been associated with treatment response in antipsychotic-naïve first episode patients. Therefore, accurate and reliable assessment is of clinical importance. Several mechanical and electronic instruments have been developed for this purpose. However, their content validity is limited. This study investigated which tasks, or combinations thereof, are most suitable for assessing bradykinesia instrumentally. Eleven motor tasks were assessed using inertial sensors. Their capability of distinguishing bradykinetic patients with schizophrenia (n = 6) from healthy controls (n = 5) was investigated. Seven tasks significantly discriminated patients from controls. The combination of tasks considered most feasible for the instrumental assessment of bradykinesia was the gait, pronation/supination, leg agility and flexion/extension of elbow tasks (effect size = 2.9).

Reliability and validity of an instrument for the assessment of bradykinesia

Bradykinesia is associated with reduced quality of life and medication non-compliance, and it may be a prodrome for schizophrenia. Therefore, screening/monitoring for subtle bradykinesia is of clinical and scientific importance. This study investigated the validity and reliability of such an instrument. Included were 70 patients with psychotic disorders. Inertial sensors captured mean cycle duration, amplitude and velocity of four movement tasks: walking, elbow flexion/extension, forearm pronation/supination and leg agility. The concurrent validity with the Unified Parkinsons Disease Rating Scale (UPDRS) bradykinesia subscale was determined using regression analysis. Reliability was investigated with the intra-class correlation coefficient. The duration, amplitude and velocities of the four tasks measured by the instrument explained 67% of the variance on the UPDRS bradykinesia subscale. The instrument test-retest reliability was high. The instrument investigated in this study is a valid and reliable alternative to observer-rated scales. It is an ideal tool for monitoring bradykinesia as it requires little training and experience to achieve reliable results.

Movement Disorders and Psychosis, a Complex Marriage

Most clinicians relate parkinsonism and dyskinesia directly to acute and tardive drug-induced movement disorders. However, parkinsonism and dyskinesia are also present in antipsychotic-naive patients with psychotic disorders. In this paper, we want to highlight the clinical value of these spontaneous movement disorders and want to discuss the concept of “non-mental signs.”

Risk Factors for Tremor in a Population of Patients with Severe Mental Illness: An 18-year Prospective Study in a Geographically Representative Sample (The Curacao Extrapyramidal Syndromes Study XI)

Background The aim was to assess incidence, prevalence and risk factors of medication-induced tremor in African-Caribbean patients with severe mental illness (SMI). Method A prospective study of SMI patients receiving care from the only mental health service of the previous Dutch Antilles. Eight clinical assessments, over 18 years, focused on movement disorders, medication use, and resting tremor (RT) and (postural) action tremor (AT). Risk factors were modeled with logistic regression for both current (having) tremor and for tremor at the next time point (developing). The latter used a time-lagged design to assess medication changes prior to a change in tremor state. Results Yearly tremor incidence rate was 2.9% and mean tremor point prevalence was 18.4%. Over a third of patients displayed tremor during the study. Of the patients, 5.2% had AT with 25% of cases persisting to the next time point, while 17.1% of patients had RT of which 65.3% persisted. When tremor data were examined in individual patients, they often had periods of tremor interspersed with periods of no tremor. Having RT was associated with age (OR=1.07 per year; 95% confidence interval 1.03–1.11), sex (OR=0.17 for males; 0.05–0.78), cocaine use (OR=10.53; 2.22–49.94), dyskinesia (OR=0.90; 0.83–0.97), and bradykinesia (OR=1.16; 1.09–1.22). Developing RT was strongly associated with previous measurement RT (OR=9.86; 3.80–25.63), with previous RT severity (OR=1.22; 1.05–1.41), and higher anticholinergic load (OR= 1.24; 1.08–1.43). Having AT was associated with tremor-inducing medication (OR= 4.54; 1.90–10.86), cocaine use (OR=14.04; 2.38–82.96), and bradykinesia (OR=1.07; 1.01–1.15). Developing AT was associated with, previous AT severity (OR=2.62 per unit; 1.64–4.18) and tremor reducing medication (OR=0.08; 0.01–0.55). Conclusions Long-stay SMI patients are prone to developing tremors, which show a relapsing–remitting course. Differentiation between RT and AT is important as risk factors differ and they require different prevention and treatment strategies.

Blink rate is associated with drug-induced parkinsonism in patients with severe mental illness, but does not meet requirements to serve as a clinical test: the Curacao extrapyramidal syndromes study XIII

BackgroundDrug-induced parkinsonism (DIP) has a high prevalence and is associated with poorer quality of life. To find a practical clinical tool to assess DIP in patients with severe mental illness (SMI), the association between blink rate and drug-induced parkinsonism (DIP) was assessed.MethodsIn a cohort of 204 SMI patients receiving care from the only mental health service of the previous Dutch Antilles, blink rate per minute during conversation was assessed by an additional trained movement disorder specialist. DIP was rated on the Unified Parkinson’s Disease Rating Scale (UPDRS) in 878 assessments over a period of 18 years. Diagnostic values of blink rate were calculated.ResultsDIP prevalence was 36%, average blink rate was 14 (standard deviation (SD) 11) for patients with DIP, and 19 (SD 14) for patients without. There was a significant association between blink rate and DIP (p < 0.001). With a blink rate cut-off of 20 blinks per minute, sensitivity was 77% and specificity was 38%. A 10% percentile cut-off model resulted in an area under the ROC curve of 0.61. A logistic prediction model between dichotomous DIP and continuous blink rate per minute an area under the ROC curve of 0.70.ConclusionsThere is a significant association between blink rate and DIP as diagnosed on the UPDRS. However, blink rate sensitivity and specificity with regard to DIP are too low to replace clinical rating scales in routine psychiatric practice.Trial registrationThe study was started over 20 years ago in 1992, at the time registering a trial was not common practice, therefore the study was never registered.