Implications of therapy interruption on monthly migraine days and modified migraine disability assessment in patients treated with erenumab for chronic and episodic migraine: SQUARE study interim results.

BACKGROUND: There are limited real-world data in Switzerland examining the impact of erenumab, a fully human IgG2 monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor, on migraine-related quality of life. OBJECTIVE: This 18-month interim analysis of 172 patients with episodic or chronic migraine from the SQUARE study provides first prospective insights on the impact of mandatory erenumab treatment interruption, following Swiss-reimbursement requirements, in a real-world clinical setting in Switzerland. FINDINGS: Recruited patients receiving 70 or 140 mg erenumab underwent treatment interruption on average 11.2 months after therapy onset with a mean duration of 4 months. There were sustained improvements in mean monthly migraine days (MMD) and migraine disability (mMIDAS) during initial treatment with erenumab. Treatment interruption was associated with a temporary worsening of condition. Symptoms ameliorated upon therapy reuptake reaching improvements similar to pre-break within 3 months. CONCLUSIONS: Treatment interruption was associated with a temporary worsening of condition, which improved again after therapy restart.

Alterations of niacin skin sensitivity in recurrent unipolar depressive disorder.

INTRODUCTION: Skin flushing after niacin (methylnicotinate, vitamin B(3)) stimulation is a biological marker of availability of polyunsaturated fatty acids (PUFA). Decreased PUFA levels have been reported in depressive disorder, while add-on supplementation of omega-3 PUFA has been suggested to improve depressive symptoms. This study aimed to clarify whether a disturbance of niacin skin flushing occurs also in depression, and to identify patient characteristics for those who might benefit from PUFA supplementation. METHOD: We studied 30 patients with recurrent unipolar depressive disorder during a major depressive episode (treated with antidepressants), and 30 healthy volunteers matched for age and gender. Aqueous methylnicotinate was applied in three dilution steps (0.001M, 0.01M, and 0.1M) onto the inner forearm skin. Skin flushing was assessed in three-minute intervals over 15min using optical reflection spectroscopy. RESULTS: While there was no overall difference in skin flushing between patients and controls, niacin sensitivity was inversely correlated with severity of symptoms, and flush deficits were significantly associated with depressed mood, feelings of anxiety and somatic symptoms (loss of appetite and weight loss). CONCLUSION: Results are suggestive of a subgroup of depressive patients characterised by a specific symptom cluster and disturbed niacin skin flushing.

Cannabinoids influence lipid-arachidonic acid pathways in schizophrenia.

Increasing evidence suggests modulating effects of cannabinoids on time of onset, severity, and outcome of schizophrenia. Efforts to discover the underlying pathomechanism have led to the assumption of gene x environment interactions, including premorbid genetical vulnerability and worsening effects of continuing cannabis use. The objective of this cross-sectional study is to investigate the relationship between delta-9-tetrahydrocannabinol intake and niacin sensitivity in schizophrenia patients and healthy controls. Intensity of niacin skin flushing, indicating disturbed prostaglandin-mediated processes, was used as peripheral marker of lipid-arachidonic acid pathways and investigated in cannabis-consuming and nonconsuming schizophrenia patients and in healthy controls. Methylnicotinate was applied in three concentrations onto the forearm skin. Flush response was assessed in 3-min intervals over 15 min using optical reflection spectroscopy. In controls, skin flushing was significantly decreased in cannabis-consuming as compared to nonconsuming individuals. When comparing the nonconsuming subgroups, patients showed significantly decreased flush response. The populations as a whole (patients and controls) showed an inverse association between skin flushing and sum scores of Symptom Check List 90-R. Results demonstrate an impact of long-term cannabis use on lipid-arachidonic acid pathways. Considering pre-existing vulnerability of lipid metabolism in schizophrenia, observed effects of cannabis use support the notion of a gene x environment interaction.

The influence of age and gender on niacin skin test results - implications for the use as a biochemical marker in schizophrenia.

Investigation of abnormal skin response to niacin (vitamin B3) stimulation has gained increasing interest in schizophrenia research during last years. However, current efforts to implement niacin tests in routine diagnostics are jeopardised by wide inter-individual variations of skin response. We investigated age and gender as potential factors of influence on niacin sensitivity in 117 healthy subjects (63 male, 54 female). Niacin was applied in three dilution steps (0.1, 0.01, 0.001 M) onto the inner forearm skin. Skin reaction was assessed in three minute intervals over 15 min using optical reflection spectroscopy. Males displayed a significantly weaker flush response than females. The rate of non-responders at the lowest concentration was about twice as high in men than women. Significant negative correlations between age and niacin sensitivity were revealed for both sexes. Age and gender considerably influence niacin sensitivity, possibly due to the effects of sex hormones on vasomotor function and prostaglandin metabolism. Consideration of gender and age is strongly recommended for further clinical niacin studies.