Dopamine D2 Partial Agonist Research Articles

Effect of Switching to Brexpiprazole on Plasma Homovanillic Acid Levels and Antipsychotic-Related Side Effects in Patients with Schizophrenia or Schizoaffective Disorder.

ObjectiveAlthough switching antipsychotics is a common strategy in the treatment of schizophrenia, caution is needed because of the risk of worsening of psychosis, particularly when switching to a dopamine D2 partial agonist. Homovanillic acid (HVA), a dopamine metabolite, is thought to be a possible indicator of the response to antipsychotics. We examined the effects of switching to brexpiprazole monotherapy from other antipsychotics on plasma HVA levels and side effects during maintenance treatment of schizophrenia.MethodsThe antipsychotics of 37 Japanese patients with schizophrenia or schizoaffective disorder were switched to brexpiprazole for the improvement of side effects. We evaluated clinical symptoms and extrapyramidal symptoms (EPS) and took fasting blood samples at baseline and endpoint (eight weeks after completing the switch) to measure plasma levels of HVA, prolactin, and metabolic parameters.ResultsSwitching to brexpiprazole significantly decreased the Drug-Induced Extrapyramidal Symptoms Scale total score (p=0.008), prolactin levels (p<0.001), body weight (p=0.046), and body-mass index (p=0.034), and increased HDL cholesterol (p=0.008). On the other hand, switching to brexpiprazole did not change plasma levels of HVA or Positive and Negative Syndrome Scale scores.ConclusionSwitching to brexpiprazole significantly improved EPS, high prolactin levels, and metabolic side effects without elevating plasma HVA levels. Brexpiprazole may stabilize dopaminergic neural transmission and could be a useful strategy to decrease the burden in patients with schizophrenia during the maintenance phase. Because of the small sample size, further studies with larger sample sizes are needed to confirm and extend our results.

Negative Symptoms in Schizophrenia: A Review and Clinical Guide for Recognition, Assessment, and Treatment.

Schizophrenia is frequently a chronic and disabling disorder, characterized by heterogeneous positive and negative symptom constellations. The objective of this review was to provide information that may be useful for clinicians treating patients with negative symptoms of schizophrenia. Negative symptoms are a core component of schizophrenia that account for a large part of the long-term disability and poor functional outcomes in patients with the disorder. The term negative symptoms describes a lessening or absence of normal behaviors and functions related to motivation and interest, or verbal/emotional expression. The negative symptom domain consists of five key constructs: blunted affect, alogia (reduction in quantity of words spoken), avolition (reduced goal-directed activity due to decreased motivation), asociality, and anhedonia (reduced experience of pleasure). Negative symptoms are common in schizophrenia; up to 60% of patients may have prominent clinically relevant negative symptoms that require treatment. Negative symptoms can occur at any point in the course of illness, although they are reported as the most common first symptom of schizophrenia. Negative symptoms can be primary symptoms, which are intrinsic to the underlying pathophysiology of schizophrenia, or secondary symptoms that are related to psychiatric or medical comorbidities, adverse effects of treatment, or environmental factors. While secondary negative symptoms can improve as a consequence of treatment to improve symptoms in other domains (ie, positive symptoms, depressive symptoms or extrapyramidal symptoms), primary negative symptoms generally do not respond well to currently available antipsychotic treatment with dopamine D2 antagonists or partial D2 agonists. Since some patients may lack insight about the presence of negative symptoms, these are generally not the reason that patients seek clinical care, and clinicians should be especially vigilant for their presence. Negative symptoms clearly constitute an unmet medical need in schizophrenia, and new and effective treatments are urgently needed.

Serum prolactin levels and sexual dysfunction in patients with schizophrenia treated with antipsychotics: comparison between aripiprazole and other atypical antipsychotics

ObjectivesAntipsychotics, even atypical ones, can induce hyperprolactinemia. Aripiprazole (APZ), a dopamine D2 partial agonist, has a unique pharmacological profile and few side effects. We investigated the incidence of hyperprolactinemia in patients with schizophrenia treated with APZ and other antipsychotics.MethodsSerum prolactin levels were measured by ELISA (enzyme-linked immunosorbent assay). A questionnaire survey was used to evaluate subjective sexual dysfunction.ResultsBased on the results of the questionnaire, approximately half (48.1%) of the patients complained of sexual dysfunction. The serum prolactin levels were significantly higher in patients with sexual dysfunction than in those without. In patients treated with antipsychotic monotherapy, the serum prolactin levels were significantly lower in patients treated with APZ than with other antipsychotics. In patients receiving 2 or more antipsychotics, the serum prolactin levels were significantly lower in patients treated with APZ-containing regimens than in patients treated with APZ-free regimens.ConclusionsTreatment with APZ did not influence the serum prolactin level, and adjunctive treatment with APZ may ameliorate the hyperprolactinemia that occurs during monotherapy with other antipsychotics.

Update on schizophrenia and bipolar disorder: focus on cariprazine.

Schizophrenia and bipolar disorder are severe psychiatric disorders that are frequently associated with persistent symptoms and significant dysfunction. While there are a multitude of psychopharmacologic agents are available for treatment of these illnesses, suboptimal response and significant adverse consequences limit their utility. Cariprazine is a new, novel antipsychotic medication with dopamine D2 and D3 partial agonist effects. Its safety and efficacy have been investigated in acute psychosis of schizophrenia, bipolar mania, bipolar depression, and unipolar depression. Efficacy has been demonstrated in schizophrenia and mania. It is unclear if cariprazine is effective in depression associated with unipolar or bipolar illness. Adverse consequences include extrapyramidal symptoms including akathisia, and various gastrointestinal symptoms. The US Food and Drug Administration (FDA) has recently approved cariprazine. This review will provide clinicians with basic information regarding the research program of cariprazine.

Which role for brexpiprazole, a new dopamine D2 partial agonist, in the treatment of schizophrenia?

ABSTRACT FROM: Correll CU, Skuban A, Ouyang J, et al . Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia: a 6-Week Randomized, Double-Blind, Placebo-Controlled Trial. Am J...

Aripiprazole once-monthly long-acting injectable for the treatment of schizophrenia

ABSTRACTIntroduction: Patient non-adherence increases the risk for relapse and the long-term care of schizophrenia. Long-acting injectable (LAI) antipsychotics can decrease this risk by ensuring adherence. An extended formulation, aripiprazole 400 mg once-monthly (AOM 400) LAI (AOM LAI), received regulatory approval in the year 2013 for the treatment of schizophrenia. AOM LAI is the first dopamine D2 partial agonist available in a long-acting formulation for the treatment of schizophrenia.Areas covered: This review covers data on the efficacy and tolerability/safety of AOM LAI. AOM LAI is a lyophilized powder of aripiprazole, with an elimination half-life of 29.9 – 46.5 days, allowing for a 4-week injection interval. Antipsychotic efficacy was documented in a 12-week double-blind trial (n = 340) and in two maintenance-of-effect trials: a 38-week trial (n = 662) and a 52-week trial (n = 403). The side effect profile is similar to that of oral aripiprazole. Adverse events (≥5% and at least twice that for placebo) were typically mild or moderate and did not lead to discontinuation: increased weight, akathisia, injection site pain and sedation. The 400 mg dose is tolerated by >90% of patients. Injection does not require additional training of health personnel or post-injection observation.Expert opinion: AOM LAI is an efficacious and well-tolerated antipsychotic treatment for schizophrenia.

C.06.04 Novel dopamine D2 partial agonists in the treatment of schizophrenia

C.06.04 Novel dopamine D2 partial agonists in the treatment of schizophrenia

Different effects of Bifeprunox, Aripiprazole, and Haloperidol on body weight gain, food and water intake, and locomotor activity in rats

Following on the success of Aripiprazole with its high clinical efficacy and minimal side effects, further antipsychotic drugs (such as Bifeprunox) have been developed based on the same dopamine D2 partial agonist pharmacological profile as Aripiprazole. However clinical trials of Bifeprunox have found differing results to that of its predecessor, without the same significant clinical efficacy. This study has therefore investigated the different effects of 10week treatment with Aripiprazole (0.75mg/kg, 3 times per day), Bifeprunox (0.8mg/kg, 3 times per day) and Haloperidol (0.1mg/kg, 3 times per day) on body weight gain, food and water intake, white fat mass, and 8week treatment on locomotor activity. Treatment with Bifeprunox was found to significantly reduce all of the measured parameters except white fat mass compared to the control group. However, Aripiprazole and Haloperidol treatment reduced water intake compared to the control, without any significant effects on the other measured parameters. These findings further demonstrate the potential pharmacological differences between Aripiprazole and Bifeprunox, and identify potential weight loss side effects and increased anxiety behaviour with Bifeprunox treatment.

Synthesis and SAR of aminothiazole fused benzazepines as selective dopamine D2 partial agonists

Dopamine (D2) partial agonists (D2PAs) have been regarded as a potential treatment for schizophrenia patients with expected better side effect profiles than currently marketed antipsychotics. Herein we report the synthesis and SAR of a series of aminothiazole fused benzazepines as selective D2 partial agonists. These compounds have good selectivity, CNS drug-like properties and tunable D2 partial agonism. One of the key compounds, 8h, has good in vitro/in vivo ADME characteristics, and is active in a rat amphetamine-induced locomotor activity model.

Successful treatment of dopamine dysregulation syndrome with dopamine D2 partial agonist antipsychotic drug

Dopamine dysregulation syndrome (DDS) consists of a series of complications such as compulsive use of dopaminergic medications, aggressive or hypomanic behaviors during excessive use, and withdrawal states characterized by dysphoria and anxiety, caused by long-term dopaminergic treatment in patients with Parkinson’s disease (PD). Although several ways to manage DDS have been suggested, there has been no established treatment that can manage DDS without deterioration of motor symptoms. In this article, we present a case of PD in whom the administration of the dopamine D2 partial agonistic antipsychotic drug aripiprazole improved DDS symptoms such as craving and compulsive behavior without worsening of motor symptoms. Considering the profile of this drug as a partial agonist at D2 receptors, it is possible that it exerts its therapeutic effect on DDS by modulating the dysfunctional dopamine system.

Treatment of refractory catatonic schizophrenia with low dose aripiprazole

This case is of 54-year-old female with catatonic schizophrenia, characterized by treatment resistance to the pharmacotherapy with olanzapine, risperidone, flunitrazepam, and ECT. Olanzapine and risperidone and flunitrazepam did not improve her catatonic and psychotic symptoms, and induced the extrapyramidal symptoms. The effects of ECT did not continue even for a month. However, the treatment with low-dose aripiprazole dramatically improved the patient’s psychotic symptoms and extrapyramidal symptoms. The mechanisms underlying the effects of low-dose aripiprazole in this case remain unclear, but unlike other antipsychotics, aripiprazole is a dopamine D2 partial agonist. In this regard, our results suggest that aripiprazole has numerous advantages, especially in cases of stuporous catatonia and a defective general status.

Development and application of an LC–MS/MS method for measuring the effect of (partial) agonists on cAMP accumulation in vitro

Cyclic-adenosine monophosphate (cAMP) plays an important role in cell signalling and is widely used as a marker for receptor activation and as a target for treating various diseases. In this paper we present the development and validation of a new method for the determination of cAMP and ATP (adenosine triphosphate) and other nucleotides in a biological system by combining zwitterionic hydrophilic interaction liquid chromatography (HILIC) and tandem mass spectrometry (MS/MS).The HILIC–MS/MS method was developed for the simultaneous quantitative analysis of cAMP and ATP, and was validated by assessment of linearity (over a range from 0.5 to 100nM for cAMP and 50nM to 50μM for ATP (r2>0.999)), resolution, limit of detection (0.5 and 50nM for cAMP and ATP, respectively) and reproducibility. Furthermore, the method was validated and applied in vitro to determine cAMP accumulation in biological samples. The effect of several dopamine D2 (partial) agonists and antagonists on cAMP accumulation was assessed by determination of the cAMP/ATP ratio in cells transfected with the human dopamine D2L receptor. Quinpirole, dopamine and ropinirole produced agonist effects on cAMP accumulation, with a potency of quinpirole>ropinirole>dopamine. Lisuride, terguride and bifeprunox were found to be partial agonists with efficacies of lisuride>terguride>bifeprunox. As expected, haloperidol, (−)-sulpiride and LY-741626 were antagonists.These results demonstrate that the present analytical method was robust, fast, sensitive, and selective. Moreover, it showed utility in determining cAMP/ATP in biological systems and the ability to study the effect of (partial) agonists and antagonists which makes it a useful tool for drug discovery.

Effectiveness of aripiprazole in a patient with presumed idiopathic Parkinson's disease and chronic paranoid schizophrenia

SEVERAL CASES OF the coexistence of schizophrenia and idiopathic Parkinson's disease (IPD) have been reported and the management of concurrent psychosis and parkinsonism has been considered as quite difficult as even atypical antipsychotics may worsen parkinsonism; conversely L-dopa may worsen psychosis.1, 2 To my knowledge, this is the first case report of successful treatment with aripiprazole in a schizophrenic patient with comorbid IPD. A 71-year-old woman with chronic schizophrenia was admitted to our department. She was diagnosed with schizophrenia at age 28. She had auditory hallucinations with voices conversing with each other and persecutory delusions but did not have mood symptoms. After brief admission at age 48, her condition was stable on thioridazine 40 mg/day and sulpiride 200 mg/day. However, at age 61, she noted the resting tremor of her left arm. She discontinued all antipsychotics for several years. But, thereafter, she experienced resting tremor of the right extremities, rigidity and postural instability. At age 69, she was diagnosed as having IPD and L-dopa/carbidopa was commenced. The treatment improved parkinsonism but exacerbated her psychosis. In addition she complained of various side-effects such as nausea and consequently discontinued it after 3 months. On admission, she had no obvious cognitive deficits (the Mini-Mental State Examination = 28/30). The results of laboratory tests and the findings of cranial magnetic resonance were normal. In 123I-metaiodobenzylguanidine myocardial scintigraphy, the average count per pixel in heart to mediastinum (H/M) ratio was decreased [H/M (early) = 1.854, H/M (late) = 1.350]. Her score on the Brief Psychiatric Rating Scale (BPRS) was 79, her stage on the Hoehn–Yahr scale was IV, and her activities-of-daily-living (ADL) rating on the Barthel index was 35. However, after she started taking aripiprazole 6 mg/day, we sometimes saw her walking by herself. Therefore, we gradually increased aripiprazole over 4 weeks to 18 mg/day. Then, her psychosis gradually improved and she wanted to be more mobile. She underwent physical therapy with successful discharge after 3 months. Her psychotic symptoms, motor function and ADL all improved without antiparkinsonian medications (BPRS = 37, Hoehn–Yahr stage = III, Barthel index = 65). She continues to do well on aripiprazole 6 months post-discharge. The number of schizophrenic patients with comorbid IPD will increase in aging patients with schizophrenia. This case suggests that aripiprazole may be useful in treating such patients (especially when L-dopa cannot be administered due to its side-effects) because aripiprazole, a dopamine D2 partial agonist, theoretically may improve hypodopaminergic activity in the nigrostriatal pathway in patients with IPD. In addition, the present patient was able to undergo physical therapy safely because aripiprazole rarely induces sedation and orthostatic hypotension due to extremely weak antagonism at α1 and H1 receptors. However, several case reports of aripiprazole in patients with psychosis associated with IPD indicate that aripiprazole worsens motor function,3, 4 partly because aripiprazole appears to bind to D2 receptors by competing with dopamine replenished by L-dopa because the binding affinity to dopamine D2 receptors of aripiprazole is higher than that of dopamine.5 It is necessary to note this when administering aripiprazole with L-dopa.

The Synthesis of a Dopamine D2 Partial Agonist for the Treatment of Schizophrenia

The synthesis of the phosphoric acid salt of dopamine D2 partial agonist 2-{4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]-butoxy}-5,6,7,9-tetrahydro-1,7,9-triaza-benzocyclohepten-8-one (1) is reported. The most prominent feature of the molecule is a seven-membered ring urea functionality that has been prepared via an efficient one-pot, three-step transformation. The original synthesis from the Medicinal Chemistry group provided precursor 13 in 10 steps and 2% overall yield, required four chromatographies and employed unsafe reagents such as 2-iodoxybenzoic acid (IBX) and HClO4. The optimized synthetic route for the preparation of phosphate salt 1 consists of 12 linear steps with a 10% overall yield. Safer and more robust reaction conditions have been developed with only one required chromatography. Another key step in the synthesis is the coupling of iodide 25 with naphthalenopiperazine 12 to provide 13. Due to the difficulty to purify this intermediate, a protocol had to be developed to obtain crude ma...

Dopamine D2High receptors moderately elevated by bifeprunox and aripiprazole

Because long-term antipsychotics elicit behavioral dopamine supersensitivity, the present study examined whether 7-9 days administration of partial dopamine D2 agonists with antipsychotic activity, bifeprunox and aripiprazole, could induce biochemical changes that suggest dopamine supersensitivity. In rats, behavioral dopamine supersensitivity is associated with increased dopamine D2(High) receptors in homogenized striata. In control rat striata, bifeprunox and aripiprazole had similar K(i) values at D2 receptors. In human cloned D2Long receptors, however, aripiprazole had a K(i) of 9.6 nM and recognized 41% of the D2 receptors to be in the D2(High) state, while the values for bifeprunox were 1.3 nM and 69%, indicating that bifeprunox had higher potency and efficacy at D2. Nine days of subcutaneously injected bifeprunox (0.25 mg/kg/day) and 7 days of aripiprazole (1.5 mg/kg) increased D2(High) receptors by 102-129% and 108-188%, respectively, although the total population of D2 receptors revealed no significant changes. The increase in D2(high) receptors induced by dopamine D2 partial agonists appear to be of smaller magnitude than those seen previously with D2 antagonist antipsychotics. Future research needs to test directly whether long-term treatment with dopamine partial agonists leads to any behavioral dopamine supersensitivity.

The atypical antipsychotic drug, aripiprazole, reverses amphetamine‐induced focused stereotypy in rats

Although the dopamine D2 partial agonist and atypical antipsychotic drug (AAPD), aripiprazole (ARPZ), has been shown to antagonize apomorphine‐induced behaviors in rats, it is unknown whether ARPZ antagonizes amphetamine (AMPH)‐induced behaviors in this species. Accordingly, this study examined effects of ARPZ on AMPH‐induced focused stereotypy in rats. Clozapine was included as a comparison AAPD. Rats were first sensitized to AMPH by 5 treatments (5.0 mg/kg, ip.) each separated by 72 hr. Subsequently, AMPH treatments continued but were followed 30 min later by ARPZ (6, 12, and 18 mg/kg, po.) or clozapine (5, 10, 20 mg/kg, po.). Focused stereotypy and locomotor activity were quantified with force‐plate actometers in 4‐hr recording sessions. Clozapine prolonged AMPH‐induced focused stereotypy and slowed the rats’ rhythmic head movements. On the other hand, ARPZ significantly reversed the expression of focused stereotypy and left intact intermediate amounts of locomotion. Thus, ARPZ behaviorally antagonized the effects of the indirect‐acting dopamine agonist AMPH, and this effect is consistent with ARPZ's D2 partial agonist properties. Supported by MH043429 &amp; HD002528.

Aripiprazole in the Treatment of Depressive and Anxiety Disorders

Despite the availability of different classes of drugs for the treatment of depressive and anxiety disorders, there are a number of clinically significant unmet needs, such as a high prevalence of treatment resistance, partial response, subsyndromal symptomatology, recurrence and relapse. With the approval of atypical antipsychotics, which are associated with a lower adverse effect burden than typical antipsychotics, consideration of their off-label use for the treatment of affective disorders and various other psychiatric disorders has become a viable option. However, consideration should be given to the US FDA black box warning indicating that atypical antipsychotics may increase mortality risk, particularly in the elderly population with dementia-related psychosis. There has been much conjecture about the utility of these atypical drugs to facilitate traditional antidepressant therapy, either in combination (from the initiation of therapy) or as adjunctive therapy (in the case of partial/incomplete response). Nevertheless, at present, available evidence from randomized, placebo-controlled trials is sparse, and a formal risk/benefit assessment of the use of these agents in a nonpsychotic patient population is not yet possible. As a representative agent from the atypical antipsychotic class with a novel mechanism of action and a relatively low adverse effect burden, aripiprazole represents an interesting potential treatment for depressive and anxiety disorders. In this review, we focus on the rationale for the use of aripiprazole in these disorders. Preclinical data suggests that aripiprazole has a number of possible mechanisms of action that may be important in the treatment of depressive and anxiety disorders. Such mechanisms include aripiprazole action at serotonin (5-HT) receptors as a 5-HT1A partial receptor agonist, a 5-HT2C partial receptor agonist and a 5-HT2A receptor antagonist. Aripiprazole also acts as a dopamine D2 partial receptor agonist, and has a possible action at adrenergic receptors. Furthermore, aripiprazole may have possible neuroprotective effects. Clinical studies demonstrate that aripiprazole may be useful in the treatment of bipolar depression, major depressive disorder, treatment-resistant depression and possibly anxiety disorders. Clinical data also suggest that aripiprazole may have a lower adverse effect burden than the other atypical drugs. Future research may confirm the potential utility of aripiprazole in the treatment of depressive and anxiety disorders.

新規抗精神病薬アリピプラゾールの処方動向―市販開始後３カ月間における処方の１２週間追跡調査―

Aripiprazole,an antipsychotic having a novel dopamine D2 partial agonist mechanism of action was launched in Japan in June 2006.Since there is still not much experience of using this new drug in Japan,we decided to find out how doctors prescribe it and whether its prescription has been affecting chlorpromazine (CP) equivalent dosages of antipsychotics and concomitant use of anticholinergics by examining antipsychotic and anticholinergic prescriptions over 12 weeks for patients who were started on aripiprazole within 3 months of approval.We also sent a questionnaire to prescribers concerning their expectations of aripiprazole and the reasons if it had been discontinued.It was found that aripiprazole was much prescribed to patients receiving a single antipsychotic medication,and the most common expectation was further improvement of hallucinations and delusions.After the 12 weeks of the follow up,the prescription of aripiprazole increased the number of antipsychotics significantly but did not affect the CP equivalent dosage and percentage of concomitantly used anticholinergics.We found that the most common reason for discontinuation of aripiprazole was insufficient effectiveness for hallucinations and delusions,but in no patient was it withdrawn due to adverse effects.It seems that a complete switch to aripiprazole takes time even though it was prescribed to patients for whom switching was relatively easy,raising the possibility of polypharmacy and prolonged administration of anticholinergics.It is thus necessary to continuously monitor the administration of aripiprazole as well as that of other antipsychotics in order to prevent polypharmacy.

Role of aripiprazole in treating mood disorders

Atypical antipsychotics have been used to treat patients with schizophrenia for many years, but now there is increasing evidence of their utility in the treatment of mood disorders. In the past few years, several atypical agents have received regulatory approval for use in mania. The evidence shows that atypical antipsychotics are effective in the treatment of manic symptoms, either alone or in combination with traditional mood stabilizers, such as lithium and divalproex. Although emerging data indicate that atypical antipsychotics will be a promising addition to those therapies that are currently available for managing patients during the maintenance phase of bipolar illness, their potential in the long-term management of bipolar disorder remains to be fully explored. Aripiprazole is a recently released antipsychotic medication that differs from other atypical antipsychotic agents by its mode of action as a dopamine D2 partial agonist. It is administered orally and has a long half-life. Randomized studies have demonstrated the efficacy of aripiprazole compared with placebo in the treatment of acute relapse of schizophrenia and schizoaffective disorder, maintenance treatment of schizophrenia, treatment of acute mania, and prevention of manic relapse in patients who responded to the drug during a manic episode. Further studies are ongoing in bipolar and unipolar depression. Aripiprazole is generally well tolerated compared with other antipsychotic medications, although commonly reported side effects include extrapyramidal symptoms and motoric activation similar to akathisia. Further studies and postmarketing data will be helpful in providing additional information regarding the comparative safety, efficacy and tolerability of aripiprazole in the treatment of affective disorders.

Aripiprazole-Induced Movement Disorder

Back to table of contents Previous article Next article Letter to the EditorFull AccessAripiprazole-Induced Movement DisorderJENNIFER L. ZACHER, Pharm.D., , and A. DANIEL HATCHETT, M.D., JENNIFER L. ZACHERSearch for more papers by this author, Pharm.D., Bolingbrook, Ill., and A. DANIEL HATCHETTSearch for more papers by this author, M.D., Brecksville, OhioPublished Online:1 Jan 2006https://doi.org/10.1176/appi.ajp.163.1.160-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Aripiprazole is a dopamine D2 partial receptor agonist (1). Trials have shown rates of extrapyramidal side effects similar to those of placebo administration, as seen with other atypical antipsychotic agents (1). Some case reports have found that atypical antipsychotics may even be helpful in treating tardive dyskinesia (2, 3). Although the occurrence of extrapyramidal symptoms seems to be less frequent with atypical antipsychotics, it is important to note that these effects can still occur. To our knowledge, only one case of aripiprazole-associated dyskinesia has been reported (4). We report a case of pseudoparkinsonism and rabbit syndrome that occurred in an antipsychotic-naive patient during treatment with aripiprazole.Ms. A was a 27-year-old woman diagnosed with bipolar I disorder. Before she received care through our clinic, her condition was maintained with 150 mg/day of extended-release bupropion, 100 mg/day of lamotrigine, and 75 mg/day of extended-release venlafaxine. She had an emergence of manic symptoms and was administered aripiprazole, 10 mg/day. Ms. A had never been treated with an antipsychotic in the past. One month later, her dose of aripiprazole was increased to 20 mg/day. During the course of the next month, she was tapered from lamotrigine and venlafaxine to consolidate her drug regimen. She was seen for follow-up, where she complained of muscle stiffness and tongue movements that had grown increasingly worse over the last 2 months. She was observed by her outpatient psychiatrist to have muscle rigidity, a masked face, a shuffling gait, and orofacial movements consistent with rabbit syndrome.It was decided to taper the aripiprazole and start ziprasidone, 60 mg b.i.d., along with benztropine, 1 mg b.i.d. Ms. A was seen 5 days later with a marked improvement in symptoms. She had no orofacial movements, decreased muscle rigidity, and only a slight tremor. At this visit, aripiprazole was completely stopped, and ziprasidone was increased to 80 mg b.i.d. Two weeks later, Ms. A was seen with no muscle rigidity or orofacial movements. Benztropine was discontinued, and her condition was maintained with ziprasidone without any reemergence of symptoms. When we evaluated these events with the probability scale of Naranjo et al., the case was ranked as a probable adverse drug reaction (5).This case illustrates that the risk of developing extrapyramidal symptoms is still present, even with the newest of atypical antipsychotics. Clinicians should vigilantly monitor all patients for the emergence of symptoms, regardless of which antipsychotic a patient is receiving.