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Neuropsychiatric Disease and Treatment 2023This meta-analysis assessed whether atypical antipsychotics (AAPs) and esketamine nasal spray (ESK-NS), which are mechanistically distinct, differ in antidepressant...
PURPOSE
This meta-analysis assessed whether atypical antipsychotics (AAPs) and esketamine nasal spray (ESK-NS), which are mechanistically distinct, differ in antidepressant outcomes.
PATIENTS AND METHODS
Data were extracted from 12 trials of ESK-NS or AAPs in depressed patients (4276) with inadequate response or resistance to conventional antidepressants. Montgomery-Åsberg Depression Rating Scale (MADRS) score reductions from baseline and response rates (≥50% reduction) were analyzed.
RESULTS
At endpoint, the estimated MADRS score reduction of pooled ESK-NS arms was greater than pooled AAP arms (+9.16 points, p < 0.0001). The reduction also was greater in the pooled control arms of the ESK-NS trials than the pooled control arms of the AAP trials (+7.57 points, p < 0.0001). The mean difference in the reductions between pooled ESK-NS and control arms was 1.87 points greater than that between pooled AAP and control arms, but this difference was not significant (95% CI: -4.49, 0.74, p = 0.16). Relative to their respective control arms, the mean difference in response rates was 25% for the pooled ESK-NS and 9% for the pooled AAP arms; the mean response rate was 16% greater in the pooled ESK-NS studies than the pooled AAP studies (p = 0.0004). Comparisons against specific AAPs showed mean differences in the MADRS score reductions at 1 week between the experimental and control arms that were numerically larger in the ESK-NS trials than in the aripiprazole trials (mean difference of 1.71 points, p = 0.06) and the brexpiprazole trials (mean difference of 2.05 points, p = 0.02).
CONCLUSION
The ESK-NS arms showed numerically larger MADRS score reductions at week-1 and endpoint, and a significantly larger response rate compared with AAP arms. Prospective studies involving direct comparisons are warranted to compare the relative efficacy between these treatment regimens.
PubMed: 38161513
DOI: 10.2147/NDT.S417027 -
The Journal of Medicine Access 2023Catatonia is a psychomotor syndrome resulting from an underlying psychiatric or medical disorder commonly observed in inpatient psychiatric units. While benzodiazepines...
Catatonia is a psychomotor syndrome resulting from an underlying psychiatric or medical disorder commonly observed in inpatient psychiatric units. While benzodiazepines and electroconvulsive therapy (ECT) are effective treatment options, the unavailability of ECT in many community psychiatric hospitals in the United States negatively affects patient outcomes. We present a 25-year-old African American male with a psychiatric diagnosis of schizophrenia complicated by malignant catatonia who was admitted to a community psychiatric hospital. He required intensive medical stabilization with supportive management, and transfer requests to ECT-equipped hospitals were initiated. While awaiting transfer for 148 days, the patient's symptoms did not fully remit with lorazepam (even with 36 mg daily in divided doses) and other psychotropic medication trials, including antipsychotics and mood stabilizers. After nearly 5 months of inpatient stay, he was successfully transferred, received ECT treatment, and experienced rapid resolution of catatonia. After discharge, to obtain three monthly sessions of maintenance ECT, he had 5-h one-way ground transportation arranged to an out-of-county ECT-equipped facility. There was no relapse in catatonia by the 2-year follow-up. This report highlights a significant healthcare disparity when attempting to manage severe catatonia within community hospital settings without access to ECT in the United States. Alternative treatments, including antipsychotics, had minimal impact on symptoms and possibly increased morbidity in this case while awaiting ECT. Treatment at our designated safety net hospital still required referral to 14 ECT-equipped hospitals before successful transfer. This case highlights the urgent need for ECT availability in more community hospitals to treat patients with refractory psychiatric conditions, including catatonia. ECT is an essential psychiatric treatment that, for certain conditions, has no appropriate alternatives. We propose that access to ECT be considered in the determination of safety net hospital systems, with improved ability to transfer patients who are suffering from treatable life-threatening mental health conditions.
PubMed: 38144544
DOI: 10.1177/27550834231220504 -
Cureus Nov 2023Many antipsychotic (AP) medications work by reducing dopamine levels. As hyperdopaminergia is known to cause psychosis, antipsychotics work to relieve these symptoms by... (Review)
Review
Many antipsychotic (AP) medications work by reducing dopamine levels. As hyperdopaminergia is known to cause psychosis, antipsychotics work to relieve these symptoms by antagonizing dopamine receptors and lowering dopamine levels. Dopamine is also a known negative modulator of the prolactin pathway, which allows for drug agents like dopamine agonists (DAs) to be incredibly effective in managing tumors that secrete excess prolactin (prolactinomas). While the effects of DAs on prolactinoma size and growth have been studied for decades, the effects of APs on prolactinoma size remain to be seen. We hope to investigate the effects of APs on prolactinomas by conducting a thorough PubMed search, including patients with diagnosed prolactinoma on concurrent AP therapy. Our search led to 27 studies with a total of 32 patients. We identified themes regarding seven antipsychotics: risperidone, haloperidol, amisulpride, thioridazine, aripiprazole, olanzapine, and clozapine. Risperidone, haloperidol, amisulpride, and thioridazine caused a significant increase in prolactin in most cases where they were used, and prolactin decreased after their discontinuation. For example, risperidone discontinuation resulted in a decrease in prolactin levels by an average of 66%, while haloperidol, amisulpride, and thioridazine discontinuation lowered prolactin by an average of 82%, 72%, and 89.7%, respectively. However, there were some exceptions in regard to risperidone, haloperidol, and thioridazine, where prolactin levels were not as severely affected. Aripiprazole, olanzapine, and clozapine all had significant reductions in prolactin levels when patients were switched from another antipsychotic, such as risperidone or haloperidol. The average percent decrease in prolactin when switched to aripiprazole was 67.65%, while it was 54.16% and 68% for olanzapine and clozapine, respectively. The effect of individual antipsychotics on prolactinoma size was difficult to ascertain, as imaging was not obtained (or indicated) after every antipsychotic switch, and many patients were taking dopamine agonists concurrently. Therefore, it would be difficult to ascertain which factor affected size more. Also, some patients received surgery or radiotherapy, which completely negated our ability to make any assertions about the effects of certain pharmacological agents. Although it is difficult to ascertain the role that antipsychotic medications play in the formation of prolactinoma, we have found that the cessation of certain antipsychotic medications may lead to a reduction in prolactin levels and possibly the presence of a measurable prolactinoma.
PubMed: 38143631
DOI: 10.7759/cureus.49342 -
Biomedicines Dec 2023Mitochondria are potential targets responsible for some drug- and xenobiotic-induced organ toxicities. However, molecular mechanisms of drug-induced mitochondrial...
Mitochondria are potential targets responsible for some drug- and xenobiotic-induced organ toxicities. However, molecular mechanisms of drug-induced mitochondrial toxicities are mostly unknown. Here, multiple in vitro assays were used to investigate the effects of 22 psychotropic drugs on mitochondrial function. The acute extracellular flux assay identified inhibitors of the electron transport chain (ETC), i.e., aripiprazole, phenytoin, and fluoxetine, an uncoupler (reserpine), substrate inhibitors (quetiapine, carbamazepine, buspirone, and tianeptine), and cytotoxic compounds (chlorpromazine and valproic acid) in HepG2 cells. Using permeabilized HepG2 cells revealed minimum effective concentrations of 66.3, 6730, 44.5, and 72.1 µM for the inhibition of complex-I-linked respiration for quetiapine, valproic acid, buspirone, and fluoxetine, respectively. Assessing complex-II-linked respiration in isolated rat liver mitochondria revealed haloperidol is an ETC inhibitor, chlorpromazine is an uncoupler in basal respiration and an ETC inhibitor under uncoupled respiration (IC = 135 µM), while olanzapine causes a mild dissipation of the membrane potential at 50 µM. This research elucidates some mechanisms of drug toxicity and provides some insight into their safety profile for clinical drug decisions.
PubMed: 38137493
DOI: 10.3390/biomedicines11123272 -
Cureus Nov 2023Priapism is a painful and emergent side effect that has been linked to some antipsychotics and other psychiatric medications, most often trazodone. This is thought to be...
Priapism is a painful and emergent side effect that has been linked to some antipsychotics and other psychiatric medications, most often trazodone. This is thought to be due to some level of alpha-1 adrenergic blockade by these medications. Aripiprazole is an atypical antipsychotic with notably weak alpha-1 adrenergic antagonism. Thus, we report on a unique case of aripiprazole-induced priapism in a patient with schizophrenia and recurrent episodes of antipsychotic-induced priapism. This study offers insight into the potential mechanism of aripiprazole-induced priapism and offers alternative medications, such as olanzapine and lumateperone, to treat the patient's ongoing psychotic disorder.
PubMed: 38111440
DOI: 10.7759/cureus.48978 -
Indian Journal of Psychiatry Oct 2023Schizophrenia causes significant neurocognitive impairment. Treatment with antipsychotics leads to improvement in psychopathology and neurocognitive functions.
BACKGROUND
Schizophrenia causes significant neurocognitive impairment. Treatment with antipsychotics leads to improvement in psychopathology and neurocognitive functions.
AIM
To see comparative effectiveness of aripiprazole and olanzapine on neurocognitive profile of patients with schizophrenia.
MATERIALS AND METHODS
This was a comparative, prospective, and interventional study. Patients with schizophrenia as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), were assessed on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and neuropsychological tests at baseline. Patients were randomly assigned to aripiprazole (10-30 mg per day, orally) and olanzapine (5-20 mg per day, orally) groups on the basis of computer-generated random table number. Patients were reassessed at 10 weeks.
RESULTS
A total of 40 patients completed the study duration of 10 weeks. At baseline, the majority of patients showed significant impairment in one or more domains of neurocognition. Both aripiprazole and olanzapine led to improvement in psychiatric symptoms as well as neurocognitive profile. Aripiprazole treatment leads to significant improvement in mental speed as compared to olanzapine. A highly significant decrease in the value of the Stroop effect indicates improvement ( = 0.000**) with aripiprazole and visual-spatial constructive ability ( < 0.001). The olanzapine group showed highly significant improvement in performance of category fluency ( < 0.01) and verbal fluency ( < 0.01).
CONCLUSION
The study concludes that aripiprazole and olanzapine have strong potential to improve specific domains of neurocognitive profile.
PubMed: 38108052
DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_303_23 -
Therapeutic Advances in... 2023Discontinuation of treatment in people with first episode psychosis (FEP) is common, but the extent to which this is related to specific adverse effects of antipsychotic...
Oral and long-acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record data.
BACKGROUND
Discontinuation of treatment in people with first episode psychosis (FEP) is common, but the extent to which this is related to specific adverse effects of antipsychotic medications is unclear.
OBJECTIVES
To investigate whether antipsychotic discontinuation is associated with the prescription of particular antipsychotics and particular adverse effects.
DESIGN
Retrospective cohort study.
METHODS
We assembled de-identified electronic health record (EHR) data from 2309 adults with FEP who received care from the South London and Maudsley NHS Foundation Trust between 1st April 2008 and 31st March 2019. Associations between antipsychotic medications, clinician-recorded side effects and treatment discontinuation were investigated across a mean follow-up period of 34.2 months using Cox regression.
RESULTS
The mean age of patients was 26.7 years and 1492 (64.6%) were male. Among first prescribed antipsychotic medications, discontinuation occurred earlier with haloperidol [hazard ratio (HR) = 2.78, 95% CI = 1.69-4.60] and quetiapine (HR = 1.43, 95% CI = 1.16-1.80) than with olanzapine. Discontinuation occurred sooner when there was evidence of extrapyramidal symptoms (HR = 1.33, 95% CI = 1.08-1.64) or sexual dysfunction (HR = 1.59, 95% CI = 1.03-2.46). Among antipsychotics prescribed at any point during treatment, lurasidone (HR = 1.40, 95% CI = 1.10-1.78) and aripiprazole (HR = 1.09, 95% CI = 1.01-1.19) were associated with earlier discontinuation than olanzapine. Conversely, clozapine (HR = 0.55, 95% CI = 0.41-0.73) and paliperidone 1-monthly (PP1M) long-acting injectable (HR = 0.80, 95% CI = 0.68-0.94) were associated with later discontinuation. Unexpectedly, for antipsychotics prescribed at any stage of treatment, sedation (HR = 0.89, 95% CI = 0.81-0.97), weight gain (HR = 0.73, 95% CI = 0.64-0.83), and multiple side effects (HR = 0.83, 95% CI = 0.76-0.90) were associated with later discontinuation.
CONCLUSION
Earlier treatment discontinuation associated with sexual or extrapyramidal side effects could be related to their rapid onset and poor tolerability. Later treatment discontinuation associated with clozapine and PP1M could be related to the relative efficacy of these treatments. These findings merit consideration when selecting antipsychotic therapy for people with FEP.
PubMed: 38107162
DOI: 10.1177/20451253231211575 -
The American Journal of Case Reports Dec 2023BACKGROUND We report the case of a 28-year-old man with comorbidity of OCD, PTSD, and DID responding to aripiprazole augmentation of clomipramine combined with...
A 28-Year-Old Man with Obsessive-Compulsive Disorder, Post-Traumatic Stress Disorder, and Dissociative Identity Disorder Responding to Aripiprazole Augmentation of Clomipramine Combined with Psychoeducation and Exposure and Response Prevention.
BACKGROUND We report the case of a 28-year-old man with comorbidity of OCD, PTSD, and DID responding to aripiprazole augmentation of clomipramine combined with psychoeducation and exposure and response prevention (ERP). CASE REPORT A 28-year-old, well-educated man presented with depression, obsessive thoughts, behavioral impulsivity, and suicidal thoughts/behavior. He was known to be stubborn and sensitive to criticism since childhood. The obsessive thoughts and compulsive behaviors also started at an early age. He had 4 past psychiatric hospitalizations, mostly for dissociative episodes and bizarre behaviors, complicated with significant anxiety and distress from traumatic experiences during doctoral study. He had no-to-minimal responses to various psychotropics and traditional Chinese medicine. A thorough assessment showed he met the diagnostic criteria for OCD, PTSD, and DID. He was then treated with clomipramine in combination with aripiprazole, plus psychoeducation and exposure and response prevention (ERP). His anxiety and irritability significantly improved within 2 months and his obsessive thoughts faded away. At 6-month follow-up, the patient achieved clinical remission. One year later, he remained stable and reported having a normal life. CONCLUSIONS The case illustrates both how impairing the comorbidity of OCD, PTSD, and DID can be and how concurrent use of tricyclic antidepressant (TCA) clomipramine and partial dopamine agonist aripiprazole, together with psychoeducation and ERP, can improve outcomes when other treatment choices fail to be effective.
Topics: Adult; Humans; Male; Aripiprazole; Clomipramine; Dissociative Identity Disorder; Obsessive-Compulsive Disorder; Stress Disorders, Post-Traumatic
PubMed: 38100391
DOI: 10.12659/AJCR.941534 -
Frontiers in Psychiatry 2023Among individuals receiving an adequate pharmacological treatment for Major Depressive Disorder (MDD), only 30% reach a full symptom recovery; the remaining 70% will...
Among individuals receiving an adequate pharmacological treatment for Major Depressive Disorder (MDD), only 30% reach a full symptom recovery; the remaining 70% will experience either a pharmacological response without remission or no response at all thus configuring treatment resistant depression (TRD). After an inadequate response to an antidepressant, possible next step options include optimizing the dose of the current antidepressant, switching to a different antidepressant, combining antidepressants, or augmenting with a non-antidepressant medication. Augmentation strategies with the most evidence-based support include atypical antipsychotics (AAs). Few data are available in literature about switching to another antipsychotic when a first augmentation trial has failed. We present a case-series of patients with unipolar treatment resistant depression who were treated with a combination of antidepressant and low dose of cariprazine after failing to respond to a first augmentation with another AA. We report data about ten patients affected by unipolar depression, visited at the outpatients unit of Mental Health Department of ASL CN2 of Bra and NA1 of Napoli (Italy). All patients failed to respond to conventional antidepressant therapy. A low dose of AA (aripiprazole, risperidone or brexpiprazole) was added for one month to the ongoing antidepressant treatment without clinical improvement. A second augmentation trial was then made with cariprazine. Seven out of ten patients were responders at the end of period, of them 1 patient reached responder status by week 2. HAM-D mean scores decreased from 23.9 ± 3.9 (baseline) to 14.8 ± 5.3 (4 weeks). Cariprazine was well tolerated, no severe side effect was observed during the trial. Our sample of treatment resistant unipolar patients showed good response to augmentation with cariprazine. Failure to a first AA-augmentation trial does not preclude response to a second one. This preliminary result requires confirmation through more rigorous studies conducted over greater samples.
PubMed: 38090698
DOI: 10.3389/fpsyt.2023.1299368 -
JMIR Formative Research Dec 2023Wearable sensors in digital health may pose a risk for skin irritation through the use of wearable patches. Little is known about how patient- and product-related...
BACKGROUND
Wearable sensors in digital health may pose a risk for skin irritation through the use of wearable patches. Little is known about how patient- and product-related factors impact the risk of skin irritation. Aripiprazole tablets with sensor (AS, Abilify MyCite; Otsuka America Pharmaceutical, Inc) is a digital medicine system indicated for the treatment of patients with schizophrenia, bipolar I disorder, and major depressive disorder. AS includes aripiprazole tablets with an embedded ingestible event marker, a wearable sensor attached to the skin through a wearable patch, a smartphone app, and a web-based portal. To continuously improve the final product, successive iterations of wearable patches were developed, including raisin patch version 4 (RP4), followed by disposable wearable sensor version 5 (DW5), and then reusable wearable sensor version 2 (RW2).
OBJECTIVE
This analysis pooled safety data from clinical studies in adult participants using the RP4, DW5, and RW2 wearable patches of AS and evaluated adverse events related to the use of wearable patches.
METHODS
Safety data from 12 studies in adults aged 18-65 years from May 2010 to August 2020 were analyzed. All studies evaluated safety, with studies less than 2 weeks also specifically examining human factors associated with the use of the components of AS. Healthy volunteers or patients with schizophrenia, bipolar I disorder, or major depressive disorder were enrolled; those who were exposed to at least 1 wearable patch were included in the safety analysis. Adverse events related to the use of a wearable patch were evaluated. Abrasions, blisters, dermatitis, discoloration, erythema, irritation, pain, pruritus, rash, and skin reactions were grouped as skin irritation events (SIEs). All statistical analyses were descriptive.
RESULTS
The analysis included 763 participants (mean [SD] age 42.6 [12.9] years; White: n=359, 47.1%; and male: n=420, 55%). Participants were healthy volunteers (n=269, 35.3%) or patients with schizophrenia (n=402, 52.7%), bipolar I disorder (n=57, 7.5%), or major depressive disorder (n=35, 4.6%). Overall, 13.6% (104/763) of the participants reported at least 1 SIE, all of which were localized to the wearable patch site. Incidence of ≥1 patch-related SIEs was seen in 18.1% (28/155), 14.2% (55/387), and 9.2% (28/306) of participants who used RP4, DW5, and RW2, respectively. Incidence of SIE-related treatment discontinuation was low, which is reported by 1.9% (3/155), 3.1% (12/387), and 1.3% (4/306) of participants who used RP4, DW5, and RW2, respectively.
CONCLUSIONS
The incidence rates of SIEs reported as the wearable patch versions evolved from RP4 through RW2 suggest that information derived from reported adverse events may have informed product design and development, which could have improved both tolerability and wearability of successive products.
TRIAL REGISTRATION
Clinicaltrials.gov NCT02091882, https://clinicaltrials.gov/study/NCT02091882; Clinicaltrials.gov NCT02404532, https://clinicaltrials.gov/study/NCT02404532; Clinicaltrials.gov NCT02722967, https://clinicaltrials.gov/study/NCT02722967; Clinicaltrials.gov NCT02219009, https://clinicaltrials.gov/study/NCT02219009; Clinicaltrials.gov NCT03568500, https://clinicaltrials.gov/study/NCT03568500; Clinicaltrials.gov NCT03892889, https://clinicaltrials.gov/study/NCT03892889.
PubMed: 38085556
DOI: 10.2196/44768