Naltrexone Augmented with Prazosin Is Highly Effective for Alcohol Use Disorder
Murray Raskind, of the VA Northwest Mental Illness Research, Education, and Clinical Center, conducted a translational proof-of-concept randomized controlled trial (RCT) of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans.
“Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD…. In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition.
They concluded: “These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for AUD. They are consistent with preclinical studies in rodent models of AUD and strengthen rationale for an adequately powered definitive RCT. “
THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA IS BECOMING CLEARER
David Lewis of U. Pittsburgh showed that the glutamate neurons in the prefrontal cortex of patients with schizophrenia are deficient in the gamma (30-50 Hz) oscillations that are responsible for normal working memory.
Not only are dendrites and spines deficient in these neurons in layer 3 of the cortex, but there is a deficit in parvalbumin GABA inhibitory neurons. The GABA enzyme GAD 67 is lower, producing less inhibition. The frontal neurons are hypoactive and there is less BDNF and oxidative phosphorylation present, yielding decreases in mitochondrial function.
Intramuscular versus Intravenous Ketamine for the Management of Treatment-Resistant Depression and Suicidal Ideation
Cristina Albott of the University of Minnesota Medical School reported relatively similar efficacy of intramuscular versus intravenous ketamine for the management of treatment-resistant depression and suicidal ideation in outpatient settings.
“Intramuscular (IM) delivery represents an underexplored and promising route of administration given its high bioavailability and low cost….Sixty-six patients underwent a series of 7 to 9 IV (n=35) or IM (n=31) administrations of 0.5mg/kg ketamine during a 21-28 day period. Both IV and IM showed similar magnitudes of improvement in depression, but surprisingly only the IM route was associated in a significant improvement in suicidal ideation in a within subjects change.”
“No adverse events occurred throughout the treatment series for either administration route…. This clinical case series provides preliminary support for the effectiveness and safety of IM compared to IV ketamine in TRD. “
Influence of Childhood Maltreatment on Morphometry and Brain Network Architecture in Bipolar Disorder
Martin Teicher of McLean Hospital, Harvard Medical School, reported on the influence of childhood maltreatment on morphometry and brain network architecture in Bipolar Disorder.
“Childhood maltreatment (MAL) is common in individuals with bipolar disorder (BP) and is associated with earlier onset, more severe course, and more comorbidities.” They found that reduced hippocampal volume and white matter alterations were present in those with a history of childhood maltreatment. They concluded that “MAL may act as a sensitizer promoting the emergence of bipolar symptoms in individuals with less severe network abnormalities” than in BP patients with no MAL.
