Remission of treatment-resistant depression with tardive akathisia with electroconvulsive therapy.

This report presents a case of drug-induced severe tardive akathisia developing after the combination of a selective serotonin reuptake inhibitor and an antipsychotic, in a woman with severe major depression. The trial and combination of multiple medications is common practice in treatment-resistant patients with depression. With the increase in the prevalence of treatment-resistant depression, adverse effects of medication such as tardive akathisia are becoming more common. Tardive akathisia persists even after the withdrawal of the causative agent and is very challenging to treat. The patient did not respond to any standard medications indicated for drug-induced akathisia. As a result, the patient became suicidal and extremely distressed with all treatment options exhausted. Guidelines on the management of drug-induced tardive akathisia are non-existent. This reflects the importance of this case study, which reveals the complete remission of both tardive akathisia and all the patient's depressive symptoms after electroconvulsive therapy . This report provides evidence of an established treatment intervention used in a new situation.

Clinical Predictors of Extrapyramidal Symptoms Associated With Aripiprazole Augmentation for the Treatment of Late-Life Depression in a Randomized Controlled Trial.

OBJECTIVE: Augmentation with aripiprazole is an effective pharmacotherapy for treatment-resistant late-life depression (LLD). However, aripiprazole can cause extrapyramidal symptoms (EPS) such as akathisia and parkinsonism; these symptoms are distressing and can contribute to treatment discontinuation. We investigated the clinical trajectories and predictors of akathisia and parkinsonism in older patients receiving aripiprazole augmentation for treatment-resistant LLD. METHODS: Between 2009 and 2013, depressed older adults who did not remit with venlafaxine were randomized to aripiprazole or placebo in a 12-week trial. Participants were 60 years or older and met DSM-IV-TR criteria for major depressive episode with at least moderate symptoms. The presence of akathisia and parkinsonism was measured at each visit using the Barnes Akathisia Scale (BAS) and Simpson-Angus Scale (SAS), respectively. In an exploratory analysis, we examined a broad set of potential clinical predictors and correlates: age, sex, ethnicity, weight, medical comorbidity, baseline anxiety severity, depression severity, concomitant medications including rescue medications, and aripiprazole dosage. RESULTS: Twenty-four (26.7%) of 90 participants randomized to aripiprazole and who had akathisia scores available developed akathisia compared to 11 (12.2%) of 90 randomized to placebo. Greater depression severity was the main predictor of treatment-emergent akathisia. Most participants who developed akathisia improved over time, especially with reductions in dosage. Fifteen (16.5%) of 91 participants taking aripiprazole and who had parkinsonism scores available developed parkinsonism, but no clinical predictors or correlates were identified. CONCLUSIONS: Akathisia is a common side effect of aripiprazole, but it is typically mild and responds to dose reduction. Patients with greater baseline depression may warrant closer monitoring for akathisia. More research is needed to understand the course and predictors of treatment-emergent EPS with antipsychotic augmentation for treatment-resistant LLD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00892047.

Low Dose Loxapine: Neuromotor Side Effects and Tolerability in Autism Spectrum Disorders.

OBJECTIVE: New and repurposed drugs are urgently needed to treat individuals with autism spectrum disorders (ASD). Loxapine (LOX) in low doses of 5-15 mg/day resembles an atypical antipsychotic (Stahl 2002 ). Our recent open pilot study of LOX found significant behavioral improvements and overall weight neutrality in 16 adolescents and adults with ASD. The present study examined an outpatient sample for LOX neuromotor tolerability. METHODS: Consecutive outpatients with Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision (DSM-IV-TR) ASD diagnoses receiving LOX were examined for tardive dyskinesia (TD) and extrapyramidal side effects (EPS) using the Dyskinesia Identification System: Condensed User Scale (DISCUS), and for akathisia using the Barnes Akathisia Rating Scale. Data were also then retrospectively extracted from clinic charts regarding age, gender, diagnoses, LOX doses, treatment duration, concomitant medications, and LOX dosage reductions. RESULTS: Thirty-four subjects (25 male, 9 female) participated. Mean age was 23.4 years at LOX initiation (range 8-52). Thirteen subjects (38.2%) received loxapine for ≥5 years. Mean LOX dose was 8.9 mg/day (range 5-30 mg) and mean duration was 4.2 years (range 0.8-13). Fourteen subjects (41.2%) received concomitant atypical antipsychotics. Benztropine was prescribed in 5 of 34 subjects (14.7%). Three subjects manifested tics at baseline, but lower final DISCUS scores. Subject 26, with Prader-Willi syndrome, manifested TD. Apart from LOX 5 mg daily he received paroxetine 40 mg daily, which reduces LOX metabolism significantly. Akathisia objective scores were positive in 6 subjects (17.6%): Subject 2 scored 3 (pacing was present also at baseline); subjects 6, 7, and 11 each scored 1; and subjects 18 and 23 each scored 2. Six of 9 subjects (66.7%) with expressive language were positive for subjective akathisia. CONCLUSIONS: Low dose LOX was well tolerated, with lower than expected TD rates. This confirms clinical resemblance to an atypical antipsychotic. Individuals with neuromuscular problems including Prader-Willi Syndrome receiving LOX require close monitoring. Further study of LOX in ASD is warranted.

Antidepressant-induced tardive syndrome: a retrospective epidemiological study.

INTRODUCTION: The impact of using antidepressant on the occurrence of tardive syndrome is rarely studied. Here we aimed to investigate the prevalence of various types of antidepressant induced tardive syndrome. METHODS: This study was conducted by means of a retrospective survey. Subjects receiving antidepressant(s) for over 6 months, but no other agents that may cause involuntary movements, were consecutively recruited. Tardive syndrome was evaluated in every included subject. Possible confounding medical conditions were carefully ruled out. RESULTS: Of the 158 included subjects, 22 (14.0 %) were found to have at least one tardive syndrome. The prevalence of subtypes of tardive syndromes was: tardive dystonia: 10.8 %, tardive dykinesia: 3.2 %, tardive tremor: 1.3 %, tardive parkinsonism: 1.3 %, tardive tics: 1.3 %, tardive sensory syndrome: 1.3 %, and tardive myoclonus: 0.6 %. Using serotonin-norepinephrine reuptake inhibitors and previous marital status significantly increase the risk of tardive syndrome. DISCUSSION: This study showed that antidepressants may induce various types of tardive syndrome, of which tardive dystonia is the predominant form. Clinicians should be cautious of this infrequent but distressing adverse effect when using antidepressants.

Efficacy and safety of ziprasidone in the treatment of first-episode psychosis: an 8-week, open-label, multicenter trial.

The aim of this study was to investigate the efficacy and safety of ziprasidone in first-episode psychosis. This was an 8-week, open-label, multicenter trial. In total, 27 patients (14 male patients, 13 female patients) with a Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition diagnosis of schizophreniform disorder, schizoaffective disorder, schizophrenia, or psychotic disorder not otherwise specified comprised the study population. The initial recommended dose of ziprasidone was 40 mg/day. Within the first 2 weeks, the dose could be increased to 120-160 mg/day depending on the patient's condition. The primary outcome variables were scores on the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression-Severity scale; secondary measures included the Calgary Depression Scale for Schizophrenia and others. To assess safety, we measured drug-related adverse events, weight, lipid variables, prolactin, and corrected QT (QTc) interval. Among the 27 enrolled participants, 16 dropped out [lack of efficacy (n = 7), loss to follow-up (n = 7), withdrawn consent (n = 1), and serious adverse event (n = 1)]. The mean total daily and endpoint doses of ziprasidone were 120.30 ± 40.34 and 131.85 ± 51.22 mg/day, respectively. The administration of ziprasidone resulted in significant improvement in the PANSS (P < 0.0001) and CGI scores (P < 0.0001) over time. Significant improvement in the Calgary Depression Scale for Schizophrenia score (P < 0.0001) was also observed at week 8. The response rate (defined as a 30% or greater decrease in the PANSS total score from baseline to last observation) was 51.85%. No significant differences in extrapyramidal symptoms rating scale scores, and lipid and prolactin levels from baseline to last observation were found. However, modest side effects regarding the incidence of extrapyramidal symptoms and hyperprolactinemia, and weight change from baseline in male patients were observed. These results indicate that ziprasidone is effective in the treatment of the positive, negative, and depressive symptoms of first-episode psychosis and has a modest side-effect burden.

Un caso de síndrome SILENT / A case of SILENT syndrome

Objetivo. Examinar el caso de un paciente con enfermedad mental afectiva y ansiosa desde la adolescencia, en tratamiento con litio, que tomó de forma irregular. A los 5 años de tomar litio empezó a presentar cuadro cerebeloso de temblor, ataxia, lenguaje escandido y deterioro paulatino de habilidades cognitivas, que persistió a lo largo de 12 años, a pesar de la suspensión del litio. Método. Presentar los datos objetivos de la historia clínica a lo largo de casi 20 años de evolución. Resultados. Analizar el cuadro clínico del paciente, en relación con el síndrome SILENT (síndrome de efecto neurotóxico irreversible por litio). Comentarios. Revisar los factores que aumentan el riesgo de toxicidad tardía por litio y hacer recomendaciones (AU)

Objective. To examine the case of a patient who suffered affective and anxious mental illness since adolescence, when he started to be treated with lithium, which he took irregularly. After five years of taking lithium, the patient started to show cerebellar tremor, ataxia, dysarthria and progressive deterioration of cognitive abilities, which lasted for twelve years despite the suspension of lithium. Methods. Objective data and the progress on the clinical history over nearly twenty years were collected. Results. An analysis was made of the clinical picture of the patient associated with SILENT syndrome (syndrome of irreversible lithium neurotoxic effect). Commentary. To review and expose the factors that increase the risk of late toxicity by lithium are determined and reviewed and recommendations made (AU)

Early intervention with second-generation antipsychotics in first-episode psychosis: results of an 8-week naturalistic study.

OBJECTIVE: The objective was to compare short-term effectiveness of aripiprazole with three other second-generation antipsychotics (SGAs) in the treatment of first-episode psychosis. METHOD: In a naturalistic, 'single-blind' design, 60 subjects experiencing their first psychotic episode were treated for 8 weeks with aripiprazole (n = 19), risperidone (n = 16), olanzapine (n = 14) or quetiapine (n = 11). Medication and dosing decisions were made by treating psychiatrists, constrained to once-a-day dosing, low initial doses and no clozapine. Weekly ratings were obtained using the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Rating Scale and Barnes Akathasia Rating Scale. Weight and vital signs were also collected weekly. RESULTS: The group presented with severe psychotic symptoms (mean baseline PANSS total score of 105.2), which were reduced rapidly (P < 0.0005). The between-group and group by time interaction terms were non-significant. Similar reductions were seen across all PANSS sub-scales. At Week 1 the mean PANSS Activation Scale score was reduced more with olanzapine than in the other groups (P < 0.002). Few instances of extrapyramidal symptoms occurred; all were sporadic and did not require treatment. Group body weight increased by 7.3% over the study. Vital signs remained unchanged. CONCLUSIONS: Early intervention with low doses of four SGAs led to rapid symptom reduction in first-episode psychotic patients with severe psychopathology. Although no clear medication advantages were observed in the short term, longer duration studies with larger samples will be required for determining efficacy, rates of compliance, relapse prevention and diminished incidence of extrapyramidal signs and symptoms.

Paliperidone extended-release tablets in patients with recently diagnosed schizophrenia.

AIM: Effective early and persistent antipsychotic treatment in recently diagnosed schizophrenia may positively impact long-term outcomes. Paliperidone extended-release (ER) was assessed in this population. METHODS: Post hoc analysis of pooled data from three 6-week, double-blind (DB), placebo-controlled, and three 1-year open-label (OL) studies of paliperidone ER in schizophrenia patients. Data stratified by time since diagnosis (< or =3 vs. >3 years). RESULTS: At DB (n = 1193) and OL baselines (n = 744), 259 (21.9%) and 188 (25.3%) patients were diagnosed < or =3 years. At DB end point, both populations improved with paliperidone ER versus placebo on Positive and Negative Syndrome Scale (PANSS) total, Clinical Global Impressions-Severity and Personal and Social Performance (PSP) scale scores (all P < 0.05). At OL end point, there were significant improvements from DB baseline in both populations on these scales (P < 0.0001), with greater improvement in the < or =3-year population on PANSS total (P < 0.001) and PSP (P < 0.001) scores. During DB treatment, only the < or =3-year population reported adverse events (AEs) in > or =5% (placebo-adjusted rate) of subjects receiving paliperidone ER: akathisia, extrapyramidal disorder not otherwise specified and somnolence. During OL treatment, akathisia and somnolence occurred more frequently (> or =5%) in the < or =3- versus >3-year population. OL study completion rates were 51.1% in < or =3-year, and 48.2% in >3-year subjects. CONCLUSIONS: Paliperidone ER significantly improved symptoms and functioning in schizophrenia patients, regardless of time since diagnosis. Recently diagnosed patients who continued treatment exhibited greater symptom reduction and functional benefit over the long term. Results also suggest that these patients may be more susceptible to certain AEs.

Increased S100B serum levels in schizophrenic patients with tardive dyskinesia: association with dyskinetic movements.

Several studies show that calcium-binding protein S100B is increased in schizophrenia and may be involved in the pathogenesis of tardive dyskinesia (TD). We therefore compared serum S100B levels in normal controls (n=60), schizophrenic patients with (n=32) and without TD (n=50). Assessments included the abnormal involuntary movement scale (AIMS) and the positive and negative syndrome scale (PANSS). Serum S100B levels were measured by enzyme-linked immunosorbent assay (ELISA). The results indicated that patients with TD had higher serum S100B levels than normals and those without TD. Serum S100B levels were positively correlated with AIMS scores in patients with TD. These data suggest that increased S100B levels may be related to neuro-degeneration, associated with TD pathophysiology.

Botulinum toxin in painful tardive dyskinesia.

An 81-year-old female patient with a 12-year history of lingual pain associated to tongue and jaw involuntary movements secondary to long-term neuroleptic intake was observed. She received several pharmacological therapies without major improvement or side effects. Treatment with botulinum toxin type A markedly benefited both pain and lingual dyskinesia.

Psychopathological and cognitive correlates of tardive dyskinesia in patients treated with neuroleptics.

Even though new cases of TD are on the decline in North America and other western countries, TD remains a public health concern for patients with chronic schizophrenia, PAD, and for nonpsychiatric patients treated with dopamine receptor antagonists. The new generation of atypical antipsychotic medications is believed to pose less risk for TD. However, identifying the cognitive and disease-related correlates of TD should equip clinicians with the necessary tools to reduce the prevalence of this iatrogenic movement disorder. No effective treatments for TD are available. This lack of effective therapy is problematic, especially in the few patients in whom the disorder causes functional impairment and other complications, and in whom it may be irreversible.

Threatening auditory hallucinations and Cotard syndrome in Parkinson disease.

Psychotic symptoms are commonly reported in patients with Parkinson disease (PD). In particular, patients experience nonthreatening visual hallucinations that can occur with insight (so called hallucinosis) or without. Auditory hallucinations are uncommon, and schizophrenialike symptoms such as pejorative and threatening auditory hallucinations and delusions that are persecutory, referential, somatic, religious, or grandiose have rarely been reported. The authors present 2 PD patients who experienced threatening auditory hallucinations, without visual hallucinations, and schizophrenialike delusions with detailed description of the clinical phenomenology including 1 patient with Cotard syndrome.

Akathisia, panic, agoraphobia, and major depression following brief exposure to metoclopramide.

Psychiatric complications from nonpsychiatric medications are common. Our understanding of these phenomena is often limited, due to the relative infrequency of their occurrence for individual agents and the complexity of the pharmacological systems involved. This case report presents a patient who developed psychiatric sequelae following the administration of metoclopramide. Akathisia, panic disorder, agoraphobia, and major depressive disorder all developed sequentially after only 2 days of exposure to metoclopramide, leading to months of disability. Dopaminergic blockade was implicated as the precipitating pharmacological event. The pharmacology of benzamides is reviewed, as is the literature concerning benzamide-induced extrapyramidal and psychiatric symptoms. Finally, potential pharmacological mechanisms regarding these complications are discussed, with particular attention to the role of interactions between dopaminergic and serotonergic systems.

Prevalence and characteristics of patients with pseudoakathisia.

Pseudoakathisia (PsA) is characterised by the typical motor features of akathisia but there is a lack of subjective awareness. A total of 153 in-patients on neuroleptic medication hospitalized in two representative wards of the Psychiatric Hospital of Attica in Athens were rated on the census date using the Rating Scale for Drug-Induced Akathisia [Barnes, Br. J. Psychiatry, 154 (1989) 672-676], the Rating Scale for Extrapyramidal Side-Effects [Simpson and Angus, Acta Psychiatr. Scand. 212 (Suppl.) (1970) 11-19] and the Abnormal Involuntary Movements Scale [US Department of Health, Education and Welfare, ECDEU Assessment Manual (1976) pp. 534-537]. Eight subjects of the total in-patient population were found to have PsA of chronic type (point prevalence 5.23%). The point-prevalence of PsA among schizophrenic patients was 4.76%. In addition to the diagnosis of chronic pseudoakathisia, five patients (62.5%) had a concurrent diagnosis of chronic parkinsonism. Among patients with PsA, significant correlations were found between parkinsonism score and current daily dose of neuroleptics or high potency neuroleptics. There is evidence of a relationship between chronic pseudoakathisia, chronic parkinsonism and daily dose of neuroleptic.