brexpiprazole and Stress-Disorders--Post-Traumatic

A cardinal feature of post-traumatic stress disorder (PTSD) is a long-lasting paradoxical alteration of memory with hypermnesia for salient traumatic cues and amnesia for peri-traumatic contextual cues. So far, pharmacological therapeutic approach of this stress-related disorder is poorly developed mainly because of the lack of animal model for this paradoxical memory alteration. Using a model that precisely recapitulates the two memory components of PTSD in mice, we tested if brexpiprazole, a new antipsychotic drug with pro-cognitive effects in rodents, may persistently prevent the expression of PTSD-like memory induced by injection of corticosterone immediately after fear conditioning. Acute administration of brexpiprazole (0.3 mg/kg) 7 days' post-trauma first blocks the expression of the maladaptive fear memory for a salient but irrelevant trauma-related cue. In addition, it enhances (with superior efficacy when compared to diazepam, prazosin, and escitalopram) memory for the traumatic context, correct predictor of the threat. This beneficial effect of brexpiprazole is overall maintained 1 week after treatment. In contrast brexpiprazole fully spares normal/adaptive cued fear memory, showing that the effect of this drug is specific to an abnormal/maladaptive (PTSD-like) fear memory of a salient cue. Finally, this treatment not only promotes the switch from PTSD-like to normal fear memory, but also normalizes most of the alterations in the hippocampal-amygdalar network activation associated with PTSD-like memory, as measured by C-Fos expression. Altogether, these preclinical data indicate that brexpiprazole could represent a new pharmacological treatment of PTSD promoting the normalization of traumatic memory.

Topics: Animals; Disease Models, Animal; Escitalopram; Fear; Mice; Quinolones; Stress Disorders, Post-Traumatic; Thiophenes

Domestic family violence (FV) is a serious problem with serious impacts on mental health of victims. One such impact is post-traumatic stress disorder (PTSD), and it can be resistant to treatment (treatment-resistant or TR). This article offers novel treatment.. Two treatment resistant case studies are described where adjunctive treatment with brexpiprazole was commenced. Possible theoretical considerations are presented to explain improvement.. Adjunctive treatment with brexpiprazole was associated with significant improvement in FV subjective and objective measures, with enhanced response to trauma therapy.. Brexpiprazole improved complex post traumatic stress disorder in FV victims and needs further evaluation.

Topics: Adult; Citalopram; Combined Modality Therapy; Desvenlafaxine Succinate; Domestic Violence; Drug Resistance; Drug Therapy, Combination; Female; Humans; Middle Aged; Psychotherapy; Quinolones; Stress Disorders, Post-Traumatic; Thiophenes

Brexpiprazole (also known as OPC-34712 or Lu-AF41156) is a novel molecular compound chemically and structurally similar to aripiprazole. This drug is currently under review by the U.S. Food and Drug Administration as a monotherapy for schizophrenia and an adjunct to antidepressant medication for major depressive disorder. Additional clinical trials include studies of brexpiprazole in attention-deficit/hyperactivity disorder and posttraumatic stress disorder, and for agitation associated with dementia of the Alzheimer's type. Brexpiprazole is an example that illustrates how pharmacological drug diversity may be translated to multipurpose uses.

Topics: Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Depressive Disorder, Major; Humans; Psychomotor Agitation; Quinolones; Schizophrenia; Stress Disorders, Post-Traumatic; Thiophenes