quetiapine-fumarate and Multiple-Sclerosis

The high efficacy of atypical antipsychotics (AAP) in treating diverse psychiatric disorders has been partly attributed to their capacity to curb neuroinflammation, a shared aspect of these diseases. These immunomodulatory properties of AAP have lately been explored in the context of multiple sclerosis (MS), an autoimmune demyelinating disease of the CNS.. This study aimed to review in vivo studies reporting on the therapeutic effects of AAP both in EAE, the main animal model of MS and in cuprizone-induced demyelination. For that matter we conducted a literature search and a screening process that eventually yielded 8 eligible studies.. All studies agreed on the efficiency of AAP to dramatically reduce EAE severity and delay its onset, while suppressing the production of numerous inflammatory cytokines. Clozapine showcased similar yet more intense effects than risperidone, quetiapine and olanzapine, significantly attenuating CD4 T cell infiltration and myeloid cell activation, while upregulating Tregs. Clozapine also downregulated chemokines responsible for the migration of immune cells in the CNS and caused dopamine receptor levels in the brain of EAE mice to rise.. Taken together, these findings unanimously attest to the anti-inflammatory and immunomodulatory properties of AAP, suggesting that their therapeutic potential expands beyond their current neuropsychiatric applications. Despite the salutary effects of AAP in MS reported in vivo, a clinical trial of clozapine on MS patients failed to confirm preclinical findings due to low acceptability of AAP and early participant withdrawal.. Although preclinical evidence unquestionably supports the multifaceted beneficial properties of AAP in MS, further investigation is required to elucidate the pharmacodynamic profile of these agents and allow for their proper clinical testing on MS patients.

Topics: Animals; Antipsychotic Agents; Clozapine; Encephalomyelitis, Autoimmune, Experimental; Humans; Mice; Multiple Sclerosis; Olanzapine; Quetiapine Fumarate

Multiple sclerosis (MS) is a central nervous system disorder that is associated with progressive oligodendrocyte and neuronal loss, axonal degeneration, and demyelination. Several medications that mitigate immune abnormalities reduce both the frequency of relapses and inflammation on magnetic resonance imaging, leading to improved outcomes for people with the relapsing-remitting form of MS. However, there are no treatments for the progressive forms of MS where neurons and axons continue to degenerate; here, neuroprotective therapies, or medications that rebuild myelin to confer axonal well-being, may be useful. Quetiapine fumarate is an atypical antipsychotic with reported remyelinating and neuroprotective properties in inflammatory and noninflammatory models of demyelination, including experimental autoimmune encephalomyelitis, and both cuprizone- and global cerebral ischemia-induced demyelination. Preclinical studies suggest that quetiapine may exert these effects by stimulating proliferation and maturation of oligodendrocytes, releasing neurotrophic factors, increasing antioxidant defences, scavenging for free radicals, and inhibiting activated microglia, astrocytes, and T lymphocytes. Additionally, quetiapine may be beneficial for psychiatric and nonpsychiatric symptoms of MS including depression, anxiety, insomnia, and possibly even pain. These data indicate that clinical trials are justified to determine the safety, tolerability, and efficacy of quetiapine fumarate in MS.

Topics: Animals; Antipsychotic Agents; Dibenzothiazepines; Humans; Multiple Sclerosis; Myelin Sheath; Quetiapine Fumarate; Treatment Outcome

The term Tourettism refers to Tourette Syndrome (TS)-like symptoms which appear secondary to a variety of both acquired and congenital neurological and neuropsychiatric disorders or following an exposure to several drugs. The association between Tourettism and Multiple Sclerosis (MS) is very rare. Only two cases of patients affected by MS who also showed a simple phonic tic and complex vocal tics respectively have been reported. The case here described reports of a 30 year-old woman affected by secondary-progressive MS who developed, 7 years after the onset of the disease, TS-like symptoms which were responsive to quetiapine. At that time her brain MRI, when compared with the previous scan, showed an increased lesion burden and an increased atrophy in the regions around Sylvian fissures. Considering recent findings on TS, the increased atrophy in these strategic brain regions could be responsible for the tics onset in our patient. At the same time, the diffuse involvement of the white matter and the progressive brain atrophy which we observed could have impaired the cortico-striato-thalamo-cortical circuits consistently implicated in the pathogenesis of TS. In conclusion, we can hypothesize that in our case Tourettism and MS could be considered causal related more than coincidentally associated.

Topics: Adult; Antipsychotic Agents; Atrophy; Basal Ganglia; Brain; Cerebral Cortex; Dibenzothiazepines; Disease Progression; Female; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Nerve Fibers, Myelinated; Neural Pathways; Quetiapine Fumarate; Thalamus; Tourette Syndrome; Treatment Outcome