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Chronic pain and depression
Published in Peter R Wilson, Paul J Watson, Jennifer A Haythornthwaite, Troels S Jensen, Clinical Pain Management, 2008
The antidepressant discontinuation syndrome is predominately characterized by the acute onset of dizziness, headache, nausea, fatigue, vomiting, ataxia, and paresthesias following abrupt discontinuation of antidepressants with serotonergic activity.127 This clinical syndrome can occur with the use of SSRIs, SNRIs, and tricyclic antidepressants. Whereas the syndrome generally occurs following abrupt discontinuation of antidepressants, clinical symptoms can emerge following dose reductions. Diagnostic criteria have been proposed as outlined in Table 18.2.128, 129 The physiologic mechanisms which mediate the clinical manifestations of this syndrome are presumably related to the rapid decline in serotonin availability, but alterations in noradrenergic and cholinergic activity could also account for some associated symptoms.130
Safety considerations for the management of cholestatic itch
Published in Expert Opinion on Drug Safety, 2021
Serotoninergic signals originated in the medulla may modulate the itch pathway by stimulating inhibitory interneurons in the spinal cord. This neurotransmitter also seems to regulate the afferent evoked stimuli that carries the pruritic sensation to the central nervous system. Despite this evidence, the hypothesis that sertraline - a selective serotonin receptor inhibitor (SSRI) - improves pruritus was initially derived from anecdotal clinical experience and was not based on physiologic data, with many mechanistic details remaining unknown. A small randomized, placebo-controlled trial including 12 patients showed that sertraline at a dose of 75–100 mg/day significantly improved itch scores by a mean of 33% after 6 weeks of treatment [66]. An additional benefit of sertraline is its action as a mood stabilizer and antidepressant which has proven to be independent to its antipruritic activity [66]. The majority of side effects reported with this medication are mild including diarrhea, insomnia and mood stability. Serotonin syndrome can be seen even when using this drug at a therapeutic dose and represents a major safety concern in clinical practice. Life-threatening manifestations include autonomic hyperactivity, neuromuscular abnormalities, and mental status changes. Antidepressant discontinuation syndrome has also been described in patients who stop sertraline abruptly and manifests clinically with sensory disturbances, insomnia, nausea, hyperarousal and a flu-like syndrome [67,68].
Animal models of major depressive disorder and the implications for drug discovery and development
Published in Expert Opinion on Drug Discovery, 2019
Konstantin A. Demin, Maxim Sysoev, Maria V. Chernysh, Anna K. Savva, Mamiko Koshiba, Edina A. Wappler-Guzzetta, Cai Song, Murilo S. De Abreu, Brian Leonard, Matthew O. Parker, Brian H. Harvey, Li Tian, Eero Vasar, Tatyana Strekalova, Tamara G. Amstislavskaya, Andrey D. Volgin, Erik T. Alpyshov, Dongmei Wang, Allan V. Kalueff
There are also other behavioral paradigms relevant to animal depression-like behavior. For example, sickness behavior (Table 2) evolves as an acute sickness reaction to an inflammatory agent, followed by gradually increasing depression-like behavior, including social withdrawal and motor retardation [92]. This effect involves cytokine signaling pathways [45,61,92] and can be induced by a wide range of pro-inflammatory agents, including polysaccharide (LPS) [45,93,94], viral mimetic polyriboinosinic-polyribocytidylic acid (Poly I:C) [95] and interferon (IFN)-α [96,97]. Some overlaps between drug withdrawal and depression also exist, and have been reported in rodents for cocaine, amphetamine, ethanol, morphine and nicotine [47,48,98]. Furthermore, similar antidepressant discontinuation syndrome exists in both clinical practice and animal models [19,99]. The translational importance of these models is supported by the fact that screening for substance abuse and various medical illnesses is performed in depressed patients in a clinical setting [100].
Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments
Published in Expert Review of Clinical Pharmacology, 2020
Kyle T. Greenway, Nicolas Garel, Lisa Jerome, Allison A. Feduccia
A significant increase in antidepressant prescription rates has been documented over the recent decades with 1 in 8 American adults estimated to have filled a prescription for an antidepressant in 2013 [35,57]. This rise is partly attributable to the increasing duration of antidepressant treatment courses [58], which some attribute to antidepressant discontinuation syndrome. That is, patients may be apprehensive about stopping antidepressants due to challenging discontinuation symptoms [59,60]. Further, if such symptoms are mistaken for a relapse of the original disorder, there may be inappropriate re-initiation of the medication [61]. Some authors argue that the rise in prescription is due to excessive biomedicalization of psychiatric illness over the preceding decades [62].