Lower Incidence Of Extrapyramidal Symptoms Research Articles

THE FIRST GENERATION AND SECOND-GENERATION ANTIPSYCHOTIC DRUGS AND THEIR PHARMACOLOGY IN TREATMENT OF SCHIZOPHRENIA

Schizophrenia is a complex and severe psychiatric disorder that affects millions of people worldwide. Antipsychotic drugs have been widely used for the treatment of schizophrenia for over 60 years. The first-generation antipsychotic drugs (FGAs) were introduced in the 1950s and revolutionized the treatment of schizophrenia. However, their use is associated with a number of adverse effects, including Extrapyramidal Symptoms (EPS) and Tardive Dyskinesia (TD). Second-generation antipsychotic drugs (SGAs), also known as atypical antipsychotics, were developed in the 1990s and have become the preferred treatment for schizophrenia due to their lower incidence of EPS and TD. They also have a broader range of therapeutic effects, such as improving negative symptoms and cognitive impairment associated with schizophrenia. This review article summarizes the pharmacology of both FGAs and SGAs, including their mechanism of action, pharmacokinetics, and adverse effects. The efficacy and safety of these drugs in the treatment of schizophrenia are also discussed. In addition, this review examines the controversy surrounding the use of SGAs and their potential metabolic side effects, such as weight gain, hyperlipidemia, and diabetes. Despite the availability of SGAs, FGAs still have a role in the treatment of schizophrenia, particularly for patients who are unresponsive to SGAs or experience intolerable side effects. Furthermore, research continues to identify new pharmacological targets and treatment strategies for schizophrenia. Understanding the pharmacology and clinical use of antipsychotic drugs is essential for optimizing the treatment of schizophrenia and improving patient outcomes.

Neuroprotective effects of olanzapine against rotenone-induced toxicity in PC12 cells.

Olanzapine is an antipsychotic drug used to treat patients with schizophrenia due to its lower incidence of extrapyramidal symptoms. Previous studies have shown that olanzapine activates AMP-activated protein kinase (AMPK), and induce autophagy in SH-SY5Y cell line. In this study, we investigated whether olanzapine protected against rotenone-induced neurotoxicity in PC12 cells. We showed that treatment with olanzapine increased the phosphorylation of AMPK in both dose- and time-dependent manners in PC12 cells. In addition, olanzapine activated autophagy and increased autophagic vacuoles. Furthermore, olanzapine pretreatment could protect PC12 cells from rotenone-induced apoptosis. Besides, olanzapine pretreatment could suppress the rotenone-induced depolarization of mitochondrial potential and thus protect the cells. Moreover, pretreatment with specific AMPK inhibitor compound C or with autophagy inhibitor 3-methyladenine impaired the protective effect of olanzapine on rotenone-treated PC12 cells. In summary, our results show for the first time that olanzapine ameliorates rotenone-induced injury by activating autophagy through AMPK pathway.

The Added Value of Liquid Antipsychotics: The Case of Quetiapine.

Background: Antipsychotic drugs are the cornerstone of schizophrenia treatment and are also indicated for other psychotic and mood disorders. Different antipsychotic drugs and their formulations are available, though liquid forms have been overlooked.MethodsHerein the added value of liquid antipsychotics is reviewed, with a focus on the recently introduced liquid quetiapine, a frequently used antipsychotic.ResultsLiquid antipsychotics are easily administrated via the preferable oral route, while compliance under supervised administration is transparent. Liquid forms could be preferred in patients with swallowing difficulties, which are common in elderly patients and often concealed. In this population, the availability of liquid antipsychotics could prevent errors in medication administration, which could possibly render caregivers labile to any harm caused to the patient. Aspiration, however, remains a risk with liquid formulations. Common errors in medication administration are the omission of treatment and alteration of solid oral formulations. Regarding quetiapine, omission of treatment could be associated with non-adherence as well as discontinuation symptoms, while alteration of extended release formulation could alter its pharmacokinetics. Mildly agitated and cooperative patients are another target population of liquid antipsychotics, which can induce fast sedation avoiding involuntary intramuscular injections. The combination of sedative properties and low incidence of extrapyramidal symptoms makes liquid quetiapine a valuable option for these patients, yet the current evidence is limited.ConclusionThe liquid form of quetiapine can facilitate pharmacotherapy of schizophrenia and can be defined as value added medicine bringing key benefits not only to the patients and caregivers but also to the health care system.

Drug-induced Extrapyramidal Symptoms Scale (DIEPSS) Serbian Language version: Inter-rater and Test-retest Reliability

Drug-induced Extrapyramidal Symptoms Scale (DIEPSS) is developed in the era of second-generation antipsychotics and is suitable for evaluation of the low incidence of extrapyramidal symptoms occurring in the treatment of atypical antipsychotics, as well as the relationship between personal and social functioning. The study was carried out at the Institute of Mental Health in Serbia in 2015 Study used the 127 DIEPSS video clips material, recorded from 1987 till 2015. Four raters performed the assessment simultaneously, individually rating one assigned item immediately after seeing the video clip. For the purpose of evaluating test-retest reliability the second assessment of the same material was performed nine months after the first assessment. Inter-rater reliability was high for each individual item, with ICCs ranging from 0.769 to 0.949. The inter-rater reliability was highest for akathisia item and lowest for dyskinesia. The test-retest reliability was high for each individual item, with ICC ranging from 0.713 to 0.935. The test-retest reliability was highest for bradykinesia item and lowest for dystonia. The Serbian version of DIEPSS has high level of inter-rater and test-retest reliability. High values of concordance rates (ICC > 0.7) for each evaluated individual item suggest that items of DIEPSS are well defined.

Risk of Extrapyramidal Adverse Events With Aripiprazole.

Aripiprazole is a unique atypical antipsychotic with partial agonist activity on the dopamine-2 (D2) receptor. This unique pharmacological profile of aripiprazole was thought to lead to a lower incidence of extrapyramidal symptoms (EPSs). However, recent case reports have alluded to an increase in the risk of EPS in aripiprazole users compared with nonusers of the drug. No epidemiologic studies to date have quantified this risk. We conducted a pharmacoepidemiologic study composed of a nested case-control study using a large health claims database (IMS Health) in the United States. In the nested case-control analysis, there were 5242 cases of EPS with 50,532 corresponding controls in the entire cohort. The odds ratio (OR) for EPS among those with any prescription of aripiprazole was 5.38 (95% confidence interval [CI], 3.03-9.57). The OR was lower among those taking 2 to 3 prescriptions (OR, 2.9; 95% CI, 1.07-7.85) but increased in those receiving greater than 4 prescriptions (OR, 8.64; 95% CI, 2.63-28.38). All risk periods were compared with those of subjects who had not used aripiprazole or other antipsychotics. For the secondary outcome of dyskinesia, the risk for aripiprazole was 8.50 (95% CI, 8.53-2.27-31.97) compared with that of nonusers. In conclusion, we found an increase in the risk of EPS and dyskinesias among users of aripiprazole.

Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials

ObjectivesWe performed an updated meta-analysis of antipsychotic treatment in patients with delirium, based on a previous meta-analysis published in 2007.MethodsIncluded in this study were randomised, placebo-controlled or usual care (UC)...

Pharmacology of JNJ-37822681, a Specific and Fast-Dissociating D2 Antagonist for the Treatment of Schizophrenia

All marketed antipsychotics act by blocking dopamine D(2) receptors. Fast dissociation from D(2) receptors may be one of the elements contributing to the lower incidence of extrapyramidal symptoms (EPS) exhibited by newer antipsychotics. Therefore, we screened for specific D(2) receptor blockers with a fast rate of dissociation. Radioligand binding experiments identified N-[1-(3,4-difluorobenzyl)piperidin-4-yl]-6-(trifluoromethyl)pyridazin-3-amine (JNJ-37822681) as a fast-dissociating D(2) ligand. Its D(2) receptor specificity was high compared with atypical antipsychotics, with little activity at receptors associated with unwanted effects [α(1), α(2), H(1), muscarinic, and 5-hydroxytryptamine (5-HT) type 2C] and for receptors that may interfere with the effects of D(2) antagonism (D(1), D(3), and 5-HT(2A)). JNJ-37822681 occupied D(2) receptors in rat brain at relatively low doses (ED(50) 0.39 mg/kg) and was effective in animal models of psychosis (e.g., inhibition of apomorphine-induced stereotypy or D-amphetamine/phencyclidine-induced hyperlocomotion). Prolactin levels increased from an ED(50) (0.17 mg/kg, peripheral D(2) receptors) close to the ED(50) required for apomorphine antagonism (0.19 mg/kg, central D(2) receptors), suggesting excellent brain disposition and minimal prolactin release at therapeutic doses. JNJ-37822681 induced catalepsy and inhibited avoidance behavior, but with a specificity margin relative to apomorphine antagonism that was larger than that obtained for haloperidol and similar to that obtained for olanzapine. This larger specificity margin (compared with haloperidol) may reflect lower EPS liability and less behavioral suppression after JNJ-37822681. JNJ-37822681 is a novel, potent, specific, centrally active, fast-dissociating D(2) antagonist with optimal brain disposition, and it is the first compound that allows the evaluation of the potential value of fast D(2) antagonism for the treatment of schizophrenia and bipolar disorder.

Aripiprazole

Oral aripiprazole (Abilify®) is an atypical antipsychotic agent that is approved worldwide for use in adult patients with schizophrenia. It is a quinolinone derivative that has a unique receptor binding profile as it exhibits both partial agonist activity at dopamine D(2) receptors and serotonin 5-HT(1A) receptors and antagonist activity at 5-HT(2A) receptors. In several well designed, randomized, clinical trials of 4-6 weeks duration, aripiprazole provided symptomatic control for patients with acute, relapsing schizophrenia or schizoaffective disorder. Furthermore, following 26 weeks' treatment, the time to relapse was significantly longer for patients with chronic, stabilized schizophrenia receiving aripiprazole compared with those receiving placebo. Using a variety of efficacy outcomes, aripiprazole showed a mixed response when evaluated against other antipsychotic agents in randomized clinical trials. Longer-term data showed that improvements in remission rates and response rates favoured aripiprazole over haloperidol, although, the time to failure to maintain a response was not significantly different between the treatment arms. On the other hand, improvements in positive and negative symptom scores mostly favoured olanzapine over aripiprazole, although, the time to all-cause treatment discontinuation was not significantly different between the two treatments. Several open-label, switching trials showed that aripiprazole provided continued control of symptoms in patients with schizophrenia or schizoaffective disorder. Using a variety of efficacy outcomes or quality-of-life scores, longer-term treatment generally favoured patients switched to receive aripiprazole compared with standard-of-care oral antipsychotics. Aripiprazole was generally well tolerated in patients with schizophrenia. In particular, its use seems to be associated with a lower incidence of extrapyramidal symptoms than haloperidol and fewer weight-gain issues than olanzapine. Aripiprazole also showed a favourable cardiovascular tolerability profile and its use was associated with a reduced risk of metabolic syndrome than placebo or olanzapine. As a consequence, aripiprazole may provide a more cost-effective treatment option compared with other atypical antipsychotics. In conclusion, oral aripiprazole provides an effective and well tolerated treatment alternative for the acute and long-term management of patients with schizophrenia.

Weight Gain and Changes in Metabolic Variables following Olanzapine Treatment in Schizophrenia and Bipolar Disorder

Antipsychotic therapy forms the cornerstone of treatment for people with severe mental illness. Second-generation (atypical) antipsychotics are associated with a significantly lower incidence of extrapyramidal symptoms than the typical, first-generation agents; however, changes in metabolic variables -- including impaired glucose metabolism, diabetes mellitus, weight gain and dyslipidaemia -- have been reported during treatment with second-generation antipsychotics. Understanding any potential link between antipsychotic treatment and the incidence of these events is complicated by the increasing prevalence of obesity and diabetes occurring in the general population and the increased risk of diabetes and changes in metabolic variables in people with schizophrenia. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose level appears to fall on a continuum, with olanzapine appearing to have a greater association than some other atypical antipsychotics. The PubMed database was used to search for publications that included any information on measures of changes in weight, body mass index (BMI) and/or metabolic variables in randomized studies of olanzapine published between 1992 and 2010. In long-term (≥48 weeks) studies of olanzapine, the mean weight gain was 5.6 kg (last observation carried forward; median exposure 573 days). The proportions of patients who gained at least 7%, 15% or 25% of their baseline weight with long-term exposure were 64%, 32% and 12%, respectively. Some studies have suggested that weight gain early during the course of olanzapine treatment may predict clinically significant weight gain following long-term exposure to the drug. Changes in metabolic variables, such as elevated indices of glucose metabolism and triglyceride level, have also been observed during treatment with olanzapine. Consensus guidelines emphasize the importance of appropriate baseline screening and ongoing monitoring of weight gain and metabolic variables for people receiving all antipsychotic treatments. Long-term weight management programmes have been shown to reduce weight gain in some patients.

Antagonism at serotonin 5-HT2A receptors modulates functional activity of frontohippocampal circuit

Several second-generation antipsychotics are characterised by a significant antagonistic effect at serotonin 5-HT(2A) receptors (5-HT(2A)R), a feature that has been associated with lower incidence of extra-pyramidal symptoms and a putative amelioration of positive and negative symptoms experienced by schizophrenic patients. However, the neurofunctional substrate of 5-HT(2A) antagonism and its exact contribution to the complex pharmacological profile of these drugs remain to be elucidated. Here, we used pharmacological magnetic resonance imaging to map the modulatory effects of the selective 5-HT(2A)R antagonist Ml00907 on the spatiotemporal patterns of brain activity elicited by acute phencyclidine (PCP) challenge in the rat. PCP is a non-competitive NMDA receptor antagonist that induces dysregulation of corticolimbic glutamatergic neurotransmission and produces cognitive impairment and psychotic-like symptoms reminiscent of those observed in schizophrenia. Pre-administration of M100907 produced focal and region-dependent attenuation of PCP-induced response in frontoseptohippocampal areas. As early studies highlighted a permissive role of 5-HT(2A)R on frontal dopamine release, the role of post-synaptic dopamine D(1) receptors on PCP-induced response was examined by using the potent antagonist SCH23390. Interestingly, SCH23390 did not affect PCP's response in any of the regions examined. This finding rules out a significant contribution of dopamine in the functional changes mapped and, indirectly, the inhibitory effect of M100907, in favour of a glutamatergic origin. Our data expand recent evidence suggesting a key role of 5-HT(2A)R in modulating glutamate-mediated cognitive performance in the prefrontal cortex and highlight the whole frontoseptohippocampal circuit as a key functional substrate of 5-HT(2A)R antagonism in normal and disease states.

Acute akathisia with quetiapine: A case report and review of literature

Quetiapine is an atypical antipsychotic which has been shown to have greater relative affinity for 5-HT2A receptors than for D2 receptors, due to which it is thought to lead to lower incidence of extrapyramidal symptoms (EPS). However, over the years literature in the form of case reports have accumulated which shows that quetiapine can lead to akathisia, especially in subjects prone to develop EPS. In this study, we report the case of a 22-year-old female who developed akathisia with quetiapine 150 mg/day, which subsided with reduction in dose. We have also reviewed the existing literature with respect to akathisia with quetiapine.

The Efficacy and Safety of Blonanserin Compared with Haloperidol in Acute-Phase Schizophrenia

Blonanserin is a novel atypical antipsychotic agent with potent dopamine D(2) and serotonin 5-HT(2) antagonist properties. It may potentially have a lower incidence of adverse events than other antipsychotic agents. To determine the efficacy and safety of three doses of blonanserin compared with placebo and haloperidol in patients with acute-phase schizophrenia. This was a 6-week, randomized, double-blind, placebo- and haloperidol-controlled, international, multicentre study. Patients with an acute exacerbation of their schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) score >/=70 and a Clinical Global Impression - Severity of Illness (CGI-S) score >/=4 ('moderately ill') [with no decrease >/=20% or >/=1 point, respectively, during the wash-out period] were randomized into one of five treatment groups (blonanserin 2.5, 5 or 10 mg, haloperidol 10 mg or placebo once daily). Patients were assessed weekly for clinical efficacy, adverse events, extrapyramidal symptoms (EPS) and drug compliance, and were assessed biweekly for other safety variables. All 307 randomized patients received at least one dose of study medication and 228 (74.3%) completed the study. The mean reduction in PANSS total score at week 6 was significantly greater with all active treatments compared with placebo (-12.58; p < 0.001); blonanserin 10 mg was significantly superior to blonanserin 2.5 mg (-30.18 vs -20.6; p < 0.001), but blonanserin 5 mg (-27.19) and haloperidol 10 mg (-28.16) were not. All active treatments showed greater efficacy against the positive symptoms of schizophrenia, and blonanserin (5 and 10 mg) was more effective against the negative symptoms than haloperidol. Blonanserin was well tolerated at all doses and there was no evidence of clinically important weight gain, orthostatic hypotension, corrected QT interval prolongation or clinically relevant changes in laboratory test results. Haloperidol caused persistent elevation in prolactin levels, but this was not seen with any dose of blonanserin throughout the study period. There was a lower incidence of EPS with blonanserin 10 mg (26.6%) than with haloperidol 10 mg (53.3%). Blonanserin was effective in the treatment of acute schizophrenia and showed greater efficacy in negative symptoms compared with placebo and haloperidol. Blonanserin was well tolerated and its safety profile compared favourably with haloperidol, particularly with respect to prolactin elevation and EPS frequency.

Quetiapine Extended Release

Quetiapine is an atypical antipsychotic agent with well established efficacy and tolerability in the acute and maintenance treatment of adults with schizophrenia. The extended-release formulation of quetiapine (quetiapine XR) was developed to provide more convenient once-daily administration, as well as allowing simple and rapid dose escalation, with the aim of improving compliance (known to be a substantial issue in patients with schizophrenia). In several short-term clinical trials, oral quetiapine XR 400-800 mg once daily was generally effective across a range of symptoms in the acute treatment of schizophrenia. As a long-term maintenance treatment, quetiapine XR prevented relapse in patients with stable disease, with significantly longer times to relapse in patients treated with quetiapine XR compared with placebo. Quetiapine XR was generally well tolerated in clinical trials. According to pooled results from three 6-week trials, events occurring in >or=5% of quetiapine XR recipients with an incidence>or=2-fold that seen in placebo recipients were dry mouth, somnolence and dizziness. A generally low incidence of extrapyramidal symptoms (EPS) is seen in quetiapine XR recipients. The most common potentially EPS-associated adverse events seen with quetiapine treatment were akathisia, restlessness and tremor. Rates of worsening of Simpson-Angus Scale and Barnes Akathisia Rating Scale scores were not dissimilar among quetiapine XR, quetiapine immediate release and placebo.

Four-Week, Double-Blind, Placebo- and Ziprasidone-Controlled Trial of Iloperidone in Patients With Acute Exacerbations of Schizophrenia

Iloperidone is a mixed D2/5-HT2 antagonist in development for treatment of schizophrenia. This trial aimed to evaluate the efficacy and safety of a fixed dose of iloperidone in patients with acute exacerbations of schizophrenia. This randomized, placebo-controlled, multicenter study comprised a 1-week titration period and a 3-week double-blind maintenance period. Eligible patients (n = 593) were randomized to iloperidone 24 mg/d, ziprasidone 160 mg/d as an active control, or placebo. Primary efficacy variable was change from baseline in the Positive and Negative Syndrome Scale Total (PANSS-T) score, using a mixed-effects model repeated measures analysis. Iloperidone demonstrated significant reduction versus placebo on the PANSS-T score (P< 0.01). Significant improvement versus placebo was also demonstrated with ziprasidone (P < 0.05). Compared with ziprasidone, iloperidone was associated with lower rates of many adverse events (AEs) that are particularly troublesome with antipsychotics, including sedation, somnolence, extrapyramidal symptoms, akathisia, agitation, and restlessness; iloperidone was associated with higher rates of weight gain, tachycardia, orthostatic hypotension, dizziness, and nasal congestion as reported as an AE. Most AEs were mild to moderate. A similar amount of QT prolongation was observed with both active treatments, although no patient had a treatment-emergent postbaseline corrected QT interval of 500 msec or greater. The incidence of clinically relevant changes in laboratory parameters was comparable between iloperidone and ziprasidone. Iloperidone was associated with a low incidence of extrapyramidal symptoms. Overall, there was improvement in akathisia with iloperidone treatment. Iloperidone treatment was effective, safe, and well tolerated in patients with acute exacerbation of schizophrenia.

Aripiprazole: What Is the Role of Dopamine D2Receptor Partial Agonism?

Aripiprazole: What Is the Role of Dopamine D₂Receptor Partial Agonism?

Risperidone-Induced Neuroleptic Malignant Syndrome in Neurodegenerative Disease

Risperidone-Induced Neuroleptic Malignant Syndrome in Neurodegenerative Disease

Evidence of Switching Antipsychotic Therapy to Improve Metabolic Disturbances

Insomnia is a highly prevalent disorder with consequences for the patient's physical and mental health, daily function, and job performance. Although the exact pathophysiology of insomnia is unknown, recent research has demonstrated that normal sleep and wakefulness are controlled by reciprocal inhibition by different brain regions. This sleep-wake control system offers multiple therapeutic targets for the treatment of insomnia; currently, most research and available hypnotic agents target gamma-aminobutyric acid (GABA) on the sleep side of the switch. Historically, drugs have evolved from benzodiazepine receptor agonists to nonbenzodiazepines to, most recently, selective extrasynaptic GABA(A) receptor agonists. However, these drugs have a differential impact on characteristics of sleep. Among the compounds that modulate the benzodiazepine-sensitive GABA(A) receptors, benzodiazepines suppress stage 3-4 sleep, whereas nonbenzodiazepines have no substantial effect on these stages of sleep. Recently, work on GABA agonists indicates that they increase stage 3-4 sleep. This has been demonstrated via sleep-stage scoring as well as with spectral analysis. Further, this increase in stage 3-4 sleep is associated with a decrease in stage 1 sleep and arousals from sleep. Thus, the GABA agonists may not simply promote sleep, but consolidate it as well. The clinical utility of the increase in slow-wave sleep and the sleep consolidation it produces warrants further investigation.

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Though it has been reported that the incidence of extrapyramidal symptoms with risperidone oral solution is lower than that for risperidone tablets,there has still been no detailed comparision of the 2 dosage forms in this respect.With this in mind,we investigated the usage of anti-parkinsonism drugs for a period of 1 month from starting to take risperidone oral solution or tablets,and compared the incidence of extrapyramidal symptoms between a risperidone oral solution group of subjects and a tablets group.The incidence of extrapyramidal symptoms for the oral solution group (4.8%) was significantly lower than that for the tablets group (23.2%)(p=0.022; χ2-test)(p=0.011; Log rank test) and the number needed to treat was 5.4.From this,we concluded that risperidone oral solution is safer to use than risperidone tablets in virew of the lower incidence of extrapyramidal symptoms.

Tardive Dystonia-Associated Prescription of Aripiprazole

Back to table of contents Previous article Next article LETTERFull AccessTardive Dystonia-Associated Prescription of AripiprazoleNarsimha R. Pinninti M.B.B.S., D.P.M., M.D.,Rajnish Mago M.D.,Adityanjee M.D.,Narsimha R. Pinninti M.B.B.S., D.P.M., M.D.Search for more papers by this author,Rajnish Mago M.D.Search for more papers by this author,Adityanjee M.D.Search for more papers by this author,Published Online:1 Jul 2006AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: Tardive dystonia is a delayed side effect of antipsychotic exposure that occurs at a frequency of 1% to 4.0%. 1 Most reports of tardive dystonia are from first-generation antipsychotics with recent case reports involving risperidone, 2 olanzapine, 3 and possibly clozapine. A MEDLINE/PubMed/Psylit search did not reveal any published reports of tardive dystonia associated with second-generation antipsychotics available in the United States, such as ziprasidone, quetiapine, or aripiprazole. We report a case of tardive dystonia following the addition of aripiprazole to a patient’s medication regimen. A 35-year-old Caucasian woman diagnosed with schizoaffective disorder—bipolar subtype, panic disorder, and alcohol abuse was stable for a year on ziprasidone (160 mg), topiramate (300 mg), trazodone (100 mg hs) and temazepam (15 mg prn) for insomnia. She was hospitalized because of a relapse of psychotic, depressive, and panic symptoms. She was treated with clonazepam for panic and venlafaxine for depression. The dose of ziprasidone was increased to 200 mg/day with minimal improvement in psychotic symptoms. Aripiprazole was started and the dose titrated to 30 mg before the psychotic symptoms resolved completely. Discharge medications were ziprasidone (200 mg), aripiprazole (30 mg), clonazepam (3 mg), benztropine (2 mg), venlafaxine XR (225 mg), topiramate (300 mg), temazepam (30 mg), and trazodone (100 mg) a day.Eight weeks after discharge she presented with 1 week of an inability to stand upright, being bent to the right, a mild degree of pain in the thoracic area, and significant emotional distress. Examination showed dystonic scoliosis of the thoracic spine with convexity to the left. No other muscle group was involved. There was no rigidity or involuntary movement in other parts of the body. She had a mild degree of akathisia. She had a history of normal birth and no associated medical problems. Aripiprazole was stopped while continuing all other medications. Within a week, akathisia subsided and in a month there was substantial improvement in dystonic symptoms. Three months later she remained free of dystonic symptoms. The above clinical presentation satisfies the diagnostic criteria for tardive dystonia by Burke et al. 4 This case reminds us that despite its name, tardive dystonia is characterized more by the chronic nature of the dystonia than by the duration of antipsychotic exposure and is known to occur weeks or even days after use of antipsychotics. 4 Medications that could be implicated in tardive dystonia in this patient are ziprasidone, aripiprazole, venlafaxine, and trazodone. A drug-interaction software did not reveal any drug interaction relevant to this case. Trazodone and ziprasidone 5 have been associated with acute but not tardive dystonias. There are no reports of dystonia with venlafaxine. The dystonia, occurring 8 weeks after adding aripiprazole, showing dramatic improvement after stopping aripiprazole despite continuing ziprasidone and trazodone, makes aripiprazole the possible etiological agent. We cannot be sure if monotherapy with aripiprazole could have caused dystonia and prior treatment with antipsychotics may have predisposed the patient to developing tardive dystonia with addition of aripiprazole. Clinicians should realize that although monotherapy has a much lower incidence of extrapyramidal symptoms, when combined with second generation antipsychotics, like aripiprazole, they are not devoid of them. This includes symptoms of tardive dystonia. Department of Psychiatry, UMDNJ School of Osteopathic Medicine, Cherry Hill, N.J.Thomas Jefferson University, Philadelphia, Pa.Schizophrenia and Psychotic Disorders Program, VA Medical Center, Minneapolis, Minn.

Aripiprazole: the evidence of its therapeutic impact in schizophrenia

An ideal antipsychotic would rapidly stabilize acute psychotic symptoms and maintain the patient, without relapse, for prolonged periods in the absence of extrapyramidal, endocrine, diabetic, or cardiovascular side effects, and without weight gain. The dopamine partial agonist aripiprazole is compared with this ideal and with conventional antipsychotics, such as haloperidol, and with atypical antipsychotics. To review the evidence for the clinical impact of aripiprazole in the treatment of patients with schizophrenia. There is clear evidence that aripiprazole is as effective as haloperidol in reducing the positive and negative symptoms of schizophrenia and schizoaffective disorder. In patients with schizophrenia, aripiprazole has been shown to stabilize acute psychotic symptoms, prevent relapse in stabilized patients, and maintain patients with schizophrenia following acute relapse. Furthermore, in common with other atypical antipsychotics, aripiprazole appears to be associated with a lower incidence of side effects than typical antipsychotics and may reduce discontinuation of drug therapy. Evidence also suggests that aripiprazole may be associated with a lower incidence of extrapyramidal symptoms than conventional antipsychotics, but further long-term studies concerning tardive dyskinesia are required. Studies on the cost effectiveness of aripiprazole, as well as the quality of life and general functioning of patients taking the drug are still required, although there is some evidence of improved quality of life. Further evidence comparing aripiprazole with other atypical antipsychotics would be welcome. In conclusion, aripiprazole is an atypical antipsychotic suitable for first-line use in patients with schizophrenia. Its clinical value in relation to other atypical antipsychotics remains to be elucidated.