Partial Dopamine Agonist Research Articles

Specific effect of a dopamine partial agonist on counterfactual learning: evidence from Gilles de la Tourette syndrome

The dopamine partial agonist aripiprazole is increasingly used to treat pathologies for which other antipsychotics are indicated because it displays fewer side effects, such as sedation and depression-like symptoms, than other dopamine receptor antagonists. Previously, we showed that aripiprazole may protect motivational function by preserving reinforcement-related signals used to sustain reward-maximization. However, the effect of aripiprazole on more cognitive facets of human reinforcement learning, such as learning from the forgone outcomes of alternative courses of action (i.e., counterfactual learning), is unknown. To test the influence of aripiprazole on counterfactual learning, we administered a reinforcement learning task that involves both direct learning from obtained outcomes and indirect learning from forgone outcomes to two groups of Gilles de la Tourette (GTS) patients, one consisting of patients who were completely unmedicated and the other consisting of patients who were receiving aripiprazole monotherapy, and to healthy subjects. We found that whereas learning performance improved in the presence of counterfactual feedback in both healthy controls and unmedicated GTS patients, this was not the case in aripiprazole-medicated GTS patients. Our results suggest that whereas aripiprazole preserves direct learning of action-outcome associations, it may impair more complex inferential processes, such as counterfactual learning from forgone outcomes, in GTS patients treated with this medication.

Formulation and evaluation of nanosized aripiprazole-loaded bionanogels using novel bio-retardant from bark of Cinnamomum verum J.Presl

The current research work aimed to formulate and evaluate the aripiprazole bionanogel using Cinnamomum verum J.Presl Syn. C. zeylanicum (Lauraceae) as bio-retardant and bio-stabilizer for transcranial delivery. Aripiprazole, a partial dopamine agonist is an antipsychotic drug used in the treatment of schizophrenia, bipolar disorder, major depressive disorder, and irritability associated with autism. The biopolymer from C. verum was isolated by addition of an optimised quantity of acetone and used as bio-retardant and bio-stabilizer to prepare aripiprazole-loaded bionanogels. The initially aripiprazole nanoparticles were prepared by addition of dextrose and dextran as a nanosized agent and various proportion of bio-polymer C. verum as bio-retardant (0.4%, 0.6%, 0.8% and 1%) and guargum (1.5% and 2%) followed by optimised cycles of sonication. The nanoparticles were incorporated uniformly into the gel under magnetic stirrer mode which was prepared by sodium alginate (100 mg), PVA (100 mg) and HPMC (100 mg) and prepared bionanogel was found as the best formulation based on comparison of mentioned parameters i.e. pH, texture, spreadability, % entrapment efficacy, preliminary determination of nano size distribution and in-vitro drug release study. FC3 (1:0.8) containing a retardant showed uniform spreadability, smooth texture and T50% of 51 h and T80% of 72 h, respectively. These formulations can be used for transcranial drug delivery to target the molecule to the brain through the layers of skin, meninges, trigeminal nerves, emissary veins, cranial bones and sutures.

Effectiveness in controlling symptoms with long-acting injectable aripiprazole

IntroductionDepot antipsychotic treatment has been a radical change in the evolution and prognosis of patients with schizophrenia. Long-acting injectable aripiprazole is an anti-psychotic dopamine partial agonist. It has a good tolerance in terms of metabolism and prolactine level.ObjetivesStudying the causes of readmission at the acute unit of Marqués de Valdecilla university hospital (HUMV) in patients treated with Long-acting injectable aripiprazole LAI 400 mg.MethodologyThis is a descriptive study which pretends to assess the causes of readmission in a sample of 30 patients (12 women, 18 men) with non-affective psychosis, which had entered the acute unit of HUMV from 1st January to 30th September 2016 because of psychotic decompensations and had been treated with long-acting injectable aripiprazole 400 mg.ResultsOut of the 30 patients there were five readmissions during the observation time. Two of them for psychotic decompensation, two because of premature abandonments, with oral aripiprazole supplementation and the last one because of desertion of injectable drug. No gender differences were observed.ConclusionsIt is necessary 15 days of oral supplementation before and after the first dose of long-acting injectable aripiprazole to ensure that adequate therapeutic levels are achieved and to avoid readmissions by misuse of the drug. One of the limitations encountered in this work would be the small sample size and limited observation time. A longer-term research may allow to find more scientific evidence to clarify the clinical safety and efficacy of long-acting injectable aripiprazole in patients with non-affective psychosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Antipsychotic adjuvant treatment in OCD

Antidepressant drugs selective inhibitors of serotonin reuptake (IRS) are the drugs effective in obsessive compulsive disorder. It has not been proven more effective none of them except clomipramine. Around 40–60% of the Patients with obsessive-compulsive disorder (OCD) remain unimproved by serotonin reuptake inhibitors (SRIs).Two cases are presented in relation to this disorder and its treatment.Twenty-three year old woman begins to present anhedonia, apathy, isolation and low mood. Treatment was initiated with escitalopram with partial improvement.Obsessive component traitsThirty year old man with obsessive clinic of years of evolution, with worsening in recent months treatment with 200 mg sertraline.In both cases treatment with oral aripiprazole it was associated with a dose of 5 mg daily with improvement in obsessive symptoms.ResultsThe efficacy of aripiprazole as adjunctive drug treatment and obsessive anxiety is observed. However, we must take into account the potential risks posed as neuroleptic malignant syndrome and QTc prolongation.ConclusionAripiprazole is an antipsychotic which has a novel mechanism of action to be a partial agonist of dopamine D2 receptors. This fact has led to its inclusion in the group of antipsychotics called third generation, also called partial dopamine agonists, dopamine stabilizers or “dopamine-serotonin modulators system.” Its most common side effects such as nausea, headaches, agitation and akathisia were observed in studies on schizophrenia, schizoaffective disorder and bipolar disorder. Unlike other atypical antipsychotics, is considered a relatively neutral drug to weight gain, hyperprolactinemia, changes in metabolic parameters and sedation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

M17. Treating Symptomatic Hyperprolactinemia in Premenopausal Women With Severe Mental Illness: Results: Of the Daamsel Clinical Trial (Dopamine Partial Agonist, Aripiprazole, for the Management of Symptomatic Elevated Prolactin)

M17. Treating Symptomatic Hyperprolactinemia in Premenopausal Women With Severe Mental Illness: Results: Of the Daamsel Clinical Trial (Dopamine Partial Agonist, Aripiprazole, for the Management of Symptomatic Elevated Prolactin)

Regulation of dopaminergic function: an [18F]-DOPA PET apomorphine challenge study in humans.

Dopaminergic function has a key role in normal brain function, dopaminergic dysfunction being implicated in numerous neuropsychiatric disorders. Animal studies show that dopaminergic stimulation regulates dopaminergic function, but it is not known whether this exists in humans. In the first study (study 1), we measured dopamine synthesis capacity (indexed as Kicer) to identify the relationship between baseline and change in Kicer under resting conditions for comparison with effects of dopaminergic stimulation. In the second study (study 2), we used a within-subjects design to test effects of dopaminergic stimulation on dopamine synthesis capacity. In study 1, eight volunteers received two 18F-DOPA scans on separate days, both at rest. In study 2, 12 healthy male volunteers received two 18F-DOPA positron emission tomographic (PET) scans after treatment with either the dopamine partial agonist apomorphine (0.03 or 0.005 mg kg−1) or placebo. In study 1, no significant correlation was found between baseline and change in dopamine synthesis capacity between scans (r=−0.57, n=8, P=0.17, two-tailed). In study 2, a significant negative correlation was found between baseline dopamine synthesis capacity and percentage change in dopamine synthesis capacity after apomorphine challenge (r=−0.71, n=12, P=0.01, two-tailed). This correlation was significantly different (P<0.01) from the correlation between baseline and change in dopamine synthesis capacity under unstimulated conditions. One-way repeated-measures analysis of variance showed a significant group (study 1/study 2) × time interaction (F(1,18)=11.5, P=0.003). Our findings suggest that regulation of dopamine synthesis capacity by apomorphine depends on baseline dopamine function, consistent with dopamine stimulation stabilizing dopaminergic function. Loss of this autoregulation may contribute to dopaminergic dysfunction in brain disorders such as schizophrenia, substance dependence, and Parkinson's disease.

Inhibitory Effects of Antidepressants on Acetylcholine-Induced Contractions in Isolated Guinea Pig Urinary Bladder Smooth Muscle

Background/Aims: To investigate the potential inhibitory effects of 18 clinically available antidepressants on acetylcholine (ACh)-induced contractions in guinea pig urinary bladder smooth muscle (UBSM) in order to predict whether they may induce voiding impairment. Methods: Concentration-response curves for ACh-induced contractions in guinea pig UBSM strips were obtained in the absence or presence of selected antidepressants. When inhibitory effects indicated competitive antagonism, pA₂ values against ACh were calculated and compared to plausible antidepressant blood concentrations. Results: ACh-induced contraction was antagonized competitively within clinical dose ranges by tricyclic antidepressants (imipramine, amitriptyline, trimipramine, clomipramine, nortriptyline, and amoxapine), maprotiline (a tetracyclic antidepressant), and mirtazapine (a noradrenergic and specific serotonergic antidepressant). ACh-induced contraction was also significantly inhibited by mianserin (a tetracyclic antidepressant), paroxetine and sertraline (serotonin-selective reuptake inhibitors, SSRIs), and duloxetine (a serotonin noradrenaline (norepinephrine) reuptake inhibitor, SNRI), albeit at concentrations that substantially exceeded clinically achievable blood levels. However, ACh-induced contractions were not significantly affected by fluvoxamine and escitalopram (SSRIs), milnacipran (an SNRI), trazodone (a serotonin 5-HT_2A receptor antagonist), sulpiride (a dopamine D₂ receptor antagonist), or aripiprazole (a dopamine partial agonist). Conclusion: These findings suggest that in addition to tricyclics, some relatively novel antidepressants such as mirtazapine can induce voiding impairment, attributed to diminished UBSM contractility from the inhibition of muscarinic receptors in the UBSM.

Aripiprazole, an Antipsychotic and Partial Dopamine Agonist, Inhibits Cancer Stem Cells and Reverses Chemoresistance.

There is a growing interest in repurposing antipsychotic dopamine antagonists for cancer treatment; however, antipsychotics are often associated with an increased risk of fatal events. The anticancer activities of aripiprazole, an antipsychotic drug with partial dopamine agonist activity and an excellent safety profile, remain unknown. The effects of aripiprazole alone or in combination with chemotherapeutic agents on the growth, sphere-forming ability and stem cell/differentiation/chemoresistance marker expression of cancer stem cells, serum-cultured cancer cells from which they were derived, and normal cells were examined. At concentrations non-toxic to normal cells, aripiprazole inhibited the growth of serum-cultured cancer cells and cancer stem cells. Furthermore, aripiprazole induced differentiation and inhibited sphere formation, as well as stem cell marker expression of cancer stem cells while inhibiting their survivin expression and sensitizing them to chemotherapeutic agents. Repurposing aripiprazole as an anticancer stem cell drug may merit further consideration.

Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose.

Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors. It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 nm at dopamine D2High receptors and 2800 nm at dopamine D2Low receptors, in the same biphasic manner as a dopamine partial agonist antipsychotic drug such as aripiprazole. The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects.

Neurological, Metabolic, and Psychiatric Adverse Events in Children and Adolescents Treated With Aripiprazole.

Aripiprazole is a partial dopamine agonist with only minor neurological and psychiatric adverse effects, making it a potential first-line drug for the treatment of psychiatric disorders. However, the evidence of its use in children and adolescents is rather sparse. The aim of this case study is to discuss adverse drug reaction (ADR) reports concerning aripiprazole-associated neurological and psychiatric events in children and adolescents. The ADR report database at Danish Medicines Agency was searched for all ADRs involving children and adolescents (<18 years) reported by the search term [aripiprazole] AND all spontaneous reports since the introduction of aripiprazole in 2003 until December 31, 2015. Nineteen case reports were included in the study and included both patients with psychotic disorders (PS group) and nonpsychotic disorders (non-PS group). The PS group consisted of 5 patients with schizophrenia and psychoses, not otherwise specified; and the non-PS group consisted of fourteen cases including autism spectrum disorders, attention deficit and hyperactivity disorder, obsessive-compulsive disorder, and Tourette syndrome. The main reported adverse effects in the non-PS group were chronic insomnia, Parkinsonism, behavioral changes psychoses, and weight gain, whereas the adverse effects in the PS group was predominantly anxiety, convulsions, and neuroleptic malignant syndrome. Although aripiprazole is considered safe and well tolerated in children and adolescents, severe adverse events as neuroleptic malignant syndrome, extreme insomnia, and suicidal behavior has been reported to health authorities. Clinicians should pay attention to these possible hazards when prescribing aripiprazole to this vulnerable group of patients.

Aripiprazole long-acting injection: promising but more evidence needed

Aripiprazole long acting injection (ALAI) is now available, and this paper aims to assist clinicians in deciding when to use ALAI. Aripiprazole is a partial dopamine agonist with low sedation, relatively favourable metabolic profile and a tendency to lower, rather than raise, prolactin. Available for over a decade, aripiprazole has been increasingly recognised by many clinicians as a useful option in the treatment of psychoses. ALAI is a suspension of crystalline aripiprazole in water which takes 5-7 days to reach steady state after an initial intramuscular injection. Monthly injections achieve steady state in four months. Studies have demonstrated that ALAI is effective in aripiprazole-responsive patients. ALAI was generally well tolerated, but more prone to cause extrapyramidal side-effects than the oral form. ALAI has not been compared with other depots. Although the recommended starting dose is 400 mg, it is likely that there will be significant inter-individual dose variation. Dose optimisation in each patient will be necessary for best effectiveness and tolerability. ALAI is currently appropriate for aripiprazole-responsive patients who need a depot, but clinicians are likely to try ALAI in patients who have been on other depots, particularly in whom weight gain and hyperprolactinaemia have been problematic.

Management of antipsychotic-induced hyperprolactinemia.

Introduction:Antipsychotics represent a large portion of the psychotropics that may induce hyperprolactinemia. Clinical psychiatric pharmacists must be adept in stratifying the relative risk of hyperprolactinemia among psychotropics, identifying patient risk factors, recognizing differential diagnoses, and recommending therapeutic alternatives and treatment strategies. High-potency, typical antipsychotics are more likely to elevate prolactin although exceptions to the rule exist.Methods:A literature search of PubMed and Google Scholar was performed to identify English language articles on the treatment of antipsychotic-induced hyperprolactinemia in humans. Methodological rigor is summarized for compiled studies in addition to feasibility and limitations of application to clinical practice.Results:There is an absence of robust evidence for the management of antipsychotic-induced hyperprolactinemia. Among the pharmacological treatments studied, aripiprazole (switching or augmentation) possessed the strongest evidence. Pharmacological treatments with less evidence encompassed dose reduction, switching to lower potency antipsychotics, and adding dopamine agonists. To date, no head-to-head studies have been published on the above approaches.Discussion:Atypical antipsychotics with low affinity for dopamine (D2) receptors, such as olanzapine, are logical alternatives for the patient experiencing drug-induced hyperprolactinemia. When augmentation is clinically preferred to switching, a viable option is the addition of a full or partial dopamine agonist, such as bromocriptine or aripiprazole, respectively. Patient-specific risk of psychiatric decompensation and the severity of symptomatic hyperprolactinemia should be weighed when formulating treatment strategies.

The digital pill

Compliance with prescription medication regimens is poor in patients who suffer from chronic conditions as well as from diseases that affect public health. It is thought that improving medication adherence can have a profound effect on patient health, though medication compliance remains a problem despite the availability of many modalities. Recently, digitalizing medication adherence was made possible by Proteus Digital Health, Inc using an ingestible sensor that emits an electric field upon digestion. This signal is detected by an externally worn adhesive monitor, which records the time at which the signal is received, along with other biometric markers such as heart rate. This system is currently under United States Food and Drug Administration (FDA) review for use in a combination pill that also contains aripiprazole, a partial dopamine agonist used for the treatment of certain serious psychiatric conditions. Digitalizing medication adherence can have tremendous applications in all fields of medicine, though issues of drug costs, patient privacy, and patient autonomy may need to be addressed.

Aripiprazole once-monthly efficacy in patients with schizophrenia. Review

Introductionlong acting injectable formulations of antipsychotics are a valuable option for patients with schizophrenia, offering continuous medication delivery and stable dosage levels. Aripiprazole once-monthly is the first dopamine partial agonist available in long acting formulation approved in Europe for Schizophrenia with excellent results so far.Aimsto conduct a current review of articles related to the use and efficacy of Aripiprazole once monthly in patients with Schizophrenia.Methodssystematic review of the literature in English using the following keywords: “aripiprazole once-monthly”, “aripiprazole long acting formulation”, “schizophrenia”. PubMed database.ResultsAripiprazole once-monthly (AOM) formulation efficacy has been proven in many studies. The importance of maintaining an oral overlap during 14 days is highlighted in all studies that have been reviewed in order to reach therapeutic level; therefore, it can be used in patients with acute decompensations. Recent studies comparing AOM versus Paliperidone Palmitate once monthly (PP) have shown that patients with AOM had greater clinical improvement and, even though both drugs were well tolerated, when Quality of Life Style Scale was analyzed an important improvement in empathy, sense of purpose, emotional interaction and curiosity in the AOM group was observed.Conclusionslong acting injectable antipsychotics increase long-term adherence treatment and reduce risk of relapse. Because of its unique mechanism of action, Aripiprazole once-monthly improves positive and negative symptoms, giving the patient an opportunity to have a better quality of life.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Treatment of schizophrenia with aripiprazole may contribute to improved functions

IntroductionThe goals with modern treatment of schizophrenia are to achieve remission of clinical symptoms, prevent relapse, and to restore the patients’ functions.Objectives/aimsThe objective of this study was to investigate the impact of treatment with the partial dopamine agonist aripiprazole on functions, measured as time spent for work or studies, in patients with schizophrenia or schizoaffective disorder.MethodsRetrospective data on employment and study activities were collected for all patients between 18–65 years with schizophrenia or schizoaffective disorder at an open care psychosis clinic in Sweden (n = 104). Possible impact of treatment with aripiprazole and of other variables, such as age, gender, and disease severity, was analysed.ResultsAmong patients who worked or studied at Day of admission (n = 36), the probability of maintaining or increasing time for work or studies was significantly higher in patients treated with aripiprazole compared with patients who were not (88% versus 53%; P = 0.020). This difference remained significant after controlling for severity of symptoms, age and sex. A secondary analysis, including all patients (independent of work or study status at Day of admission) also showed a significant difference in favour of aripiprazole (53% versus 26%, P = 0.005).ConclusionsThe results indicate that patients treated with aripiprazole (monotherapy or add-on) have higher probability of maintaining functional capacity. A plausible explanation might be aripiprazole's favourable effect on cognitive functions.Disclosure of interestThe authors have not supplied their declaration of competing interest.

P.2.020 The novel antipsychotic brexpiprazole partly reverses a disruption of thalamocortical function induced by phencyclidine

Dopaminergic dysfunction is thought to be central to schizophrenia symptomatology. Previous meta-analyses of prodopaminergic drugs in schizophrenia have important limitations, and also did not include dopamine D2/D3 partial agonists. We investigated the effect of medications which increase dopamine signalling on schizophrenia symptoms by meta-analysing double-blind, placebo-controlled RCTs. 59 RCTs were included: 29 of prodopaminergic treatments, 30 of partial agonists. Partial agonists were significantly superior to placebo against positive (SMD=−0.33,p = 1.2 ×10-17), negative (SMD=−0.29,p = 2.2 × 10-31) and total symptoms (SMD =−0.39,p = 1.7 × 10-30) in schizophrenia. There were no significant differences between pooled pro-dopaminergic drugs and placebo in any symptom domain. In subgroup analysis of five studies where patients were selected for negative symptom severity, ar/modafinil was superior to placebo against negative symptoms (SMD=−0.34,p = 0.037). These data favour the clinical use of partial agonists for negative symptoms in schizophrenia, with clinically meaningful effect sizes. Our findings also suggest a benefit for ar/modafinil in patients with predominant negative symptoms. Future trials of other prodopaminergic therapies and dopamine partial agonists in patients with predominant negative symptoms are warranted.

Management of a microprolactinoma with aripiprazole in a woman with cabergoline-induced mania.

SummaryA previously healthy 32-year-old woman developed cyclical mood swings after being prescribed cabergoline for a pituitary microprolactinoma. These mood swings persisted for over 2 years, at which point she developed an acute manic episode with psychotic features and was admitted to a psychiatry unit. Cabergoline was discontinued and replaced with aripiprazole 10 mg/day. Her manic episode quickly resolved, and she was discharged within 6 days of admission. The aripiprazole suppressed her prolactin levels for over 18 months of follow-up, even after the dose was lowered to 2 mg/day. There was no significant change in tumor size over 15 months and treatment was well tolerated. However, after 9 months of taking 2 mg aripiprazole, she developed brief manic symptoms, and the dose was returned to 10 mg daily, with good effect.Learning points Dopamine agonists such as cabergoline, which are a standard treatment for microprolactinomas, can have serious adverse effects such as psychosis or valvular heart disease.Aripiprazole is a well-tolerated atypical antipsychotic that, unlike other antipsychotics, is a partial dopamine agonist capable of suppressing prolactin levels.Adjunctive, low-dose aripiprazole has been utilized to reverse risperidone-induced hyperprolactinemia.This case report demonstrates how aripiprazole monotherapy, in doses ranging from 2 to 10 mg/day, was effective in suppressing prolactin in a woman with a microprolactinoma who developed psychiatric side effects from cabergoline.

A Comparative Study of Sexual Dysfunction in Schizophrenia Patients Taking Aripiprazole Versus Risperidone

Sexual dysfunction due to antipsychotics is a significant problem encountered with first-generation antipsychotics. Even the second-generation antipsychotics like risperidone are not free of sexual dysfunction due to its D2 blocking properties leading to hyperprolactinaemia. Newer antipsychotic aripiprazole, partial dopamine agonist, with neutral effect on prolactin level or even decreasing it, is associated with avoidance of sexual dysfunction. To assess the effect of risperidone and aripiprazole on sexual function of schizophrenic patients. This was an open-label, cross-sectional, observational study conducted at College of Medical Sciences, Bharatpur. Schizophrenic patients attending OPD and inpatient, taking risperidone or aripiprazole for at least two months were included in this study. Forty one patients, without chronic medical illness and sexual dysfunction before starting drugs, with informed consent were studied during Jan 2012 and Aug 2012. Changes in sexual activity was found in 11(55%) of those taking risperidone while, only 3(14.3%) had any kind of sexual difficulty. This was statistically significant (p=0.006). Majority, 92.7% of the patients did not report about changes in sexual activity spontaneously. Sexual dysfunction was statistically significantly higher in those taking risperidone. Prevalence of sexual dysfunction was low with aripiprazole. Except those having poor sexual functions due to the drugs, the majority had to be specifically inquired about the effects of drug on sex life.

Dopamine supersensitivity psychosis and dopamine partial agonist: a retrospective survey of failure of switching to aripiprazole in schizophrenia.

The administration of aripiprazole (ARI), a dopamine partial agonist, could provoke abrupt psychotic worsening in patients with schizophrenia. We explored the relationship between this psychotic worsening and dopamine supersensitivity psychosis (DSP), which is a clinically vulnerable state. We conducted a retrospective investigation for 264 patients whose treatment medication was switched to ARI from other antipsychotics. We divided the patients into the DSP(+) group with a history of DSP episode(s) (N = 70) and the DSP(–) group without such a history (N = 194), and then compared the clinical factors relevant to the success or failure of the switch to ARI between them. The results revealed that patients in the DSP(+) group experienced psychotic worsening following the switch to ARI with a significant higher rate compared to the DSP(–) group (23% vs. 8%, P < 0.01). Moreover, the dosages of the drugs before the ARI introduction in the patients experiencing the psychotic worsening in the DSP (-) group were higher than those in other patients of the group. Our findings suggest that patients who receive high dosages of antipsychotic drugs form overt or covert DSP and such state is highly associated with psychotic worsening following ARI treatment.

Dopamine receptor partial agonists and addiction

Many drugs abused by humans acutely facilitate, either directly or indirectly, dopamine neurotransmission in the mesolimbic pathway. As a consequence dopamine receptor agonists and antagonists have been widely investigated as putative pharmacological therapies for addiction. This general strategy, however, has had only limited success due in part to poor treatment adherence and efficacy and the significant adverse effects of dopaminergic medications. In this perspective, we discuss the potential therapeutic use of dopamine receptor partial agonists in addiction, developed initially as antipsychotic agents. Recent research indicates that the dopamine D2 receptor partial agonists, such as aripiprazole, also shows useful ancillary efficacy in several animal models of psychostimulant and opioid addiction. Notably, these findings suggest that unlike full dopamine receptor agonists and antagonists these compounds have low abuse liability and are generally well tolerated. Indeed, partial dopamine agonists attenuate the rewarding properties of opioids without interfering with their analgesic effects. Herein we discuss the utility and potential of dopamine receptor partial agonists as treatments for both stimulant and non-stimulant drug addiction.