The Serotonin Subtype of Depression
Mark S. Gold, R. Bruce Lydiard, John S. Carman in Advances in Psychopharmacology: Predicting and Improving Treatment Response, 2018
Tricyclic antidepressants have been used for years as the primary treatment for major depressive illness. These agents act by blocking neurotransmitter reuptake from the synapse16 and affect both serotonin and norepinephrine neurons. Researchers have proposed the idea that these are two distinct subgroups of depression, characterized by norepinephrine or serotonin deficiencies, respectively.45 Norepinephrine-deficient depressions have been associated with low CSF MHPG levels, while serotonin-deficient depressions are associated with low CSF 5-HIAA levels. The differentiation of these two subsets of depression has led investigators to explore their responsivity to specific tricyclic antidepressants. Pretreatment levels of CSF 5-HIAA and MHPG have been assessed with respect to predictability of response to antidepressants with either serotonin or norepinephrine mechanisms.
Recent Advances in Repositioning Non-Antibiotics against Tuberculosis and other Neglected Tropical Diseases
Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay in Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Tricyclic antidepressants and selective serotonin reuptake inhibitors: Antidepressant drugs are the mainstay for major depressive disorder and elicit their effects through blocking the reuptake of serotonin as well as norepinephrine. The majority of these antidepressants bear structural resemblance to phenothiazines (Krystal 2011). Godbole et al. docked libraries of FDA approved drugs into the homology model for Mtb topoisomerase I, an enzyme responsible for maintaining genome topology during DNA replication and transcription. From this in silico screening, compounds with a favourable docking score including imipramine 45 and norclomipramine 46 were selected for further evaluation against Mtb (Figure 3). Both drugs displayed some antimycobacterial activity against Mtb (MIC 250 μM and 60 μM, respectively) and also inhibitory effects against the topoisomerase enzyme. Moreover, imipramine acted synergistically with moxifloxacin, a well-known type II topoisomerase inhibitor (Godbole et al. 2015). The antitubercular effects of selective reuptake inhibitors, fluoxetine 47 (MIC 69.4 μM) and sertraline 48 (MIC 59.0 μM), have also been demonstrated (Figure 3). Both antidepressants displayed a dose-dependent growth restriction of Mtb after 72 hr treatment in resting primary murine macrophages. The study also showed that accumulation of protonatable forms of the drugs in macrophages is partially pH-dependent (Schump et al. 2017).
Diabetic Neuropathy
Jack L. Leahy, Nathaniel G. Clark, William T. Cefalu in Medical Management of Diabetes Mellitus, 2000
Amitriptyline is a popular first-line therapy because of its efficacy, low cost, ease of use (at bedtime), and predictable side effect profile. Patients may respond to doses as low as 25 mg at night, but usually amounts between 50 and 150 mg are needed to achieve acceptable analgesia. A dose-benefit relations exists for amitriptyline, with higher dosages producing greater pain relief. A starting dose of 10 mg is advisable in elderly patients because of their sensitivity to tricyclic antidepressants and potential interaction with other drugs prescribed for coexisting conditions. Common side effects reported by patients taking tricyclic antidepressants are drowsiness, dry eyes and mouth, constipation, weight gain, and increased appetite. The efficacy of amitriptyline for neuropathic pain appears to be separate from its effect on depression (19). Max et al. reported that amitriptyline-induced analgesia was similar in patients with diabetic neuropathy who were depressed or nondepressed and the benefit was not associated with mood improvement (19). The same authors showed that desipramine was equally as effective as amitriptyline in the treatment of painful diabetic neuropathy, yet the selective blocker of serotonin reuptake, fluoxetine, was no more effective than placebo for the relief of pain (20). Of interest, 41% of subjects in that study receiving placebo reported pain relief. Other tricyclic antidepressants that have been used with success include imipramine, nortriptyline, and doxepin (21).
Depression during pregnancy amidst COVID-19
Published in Hospital Practice, 2021
Balaji Subramanian Srinivasa Sekaran, Steven Lippmann
The most commonly recommended SSRI medications during pregnancy are sertraline, citalopram, fluvoxamine, paroxetine, escitalopram, and fluoxetine; less data is documented for others in this class [7]. Concerns about the cardiac development-safety of prescribing paroxetine are not fully understood, but it is sometimes considered as a possible pharmacotherapeutic option [7]. Prescribing duloxetine and venlafaxine NSRIs is reported to be safe [8]. Yet, there remain issues, changes in indications or efficacy, safety ratings, and restrictions involving SSRI and NSRI prescribing; drugs within each class have different actions. QT prolongation remains a concern with citalopram and escitalopram, questions about the effectiveness of duloxetine, and there are numerous reviews about these medicines [7,9–11]; these have sometimes resulted in changing patterns of prescribing, for example, with more reliance on sertraline and venlafaxine and less for paroxetine. Tricyclic antidepressant medicines have a long-known efficacy. Monotherapy with any of these agents is preferred. Higher dosages are sometimes needed later in pregnancy. Sustained, consistent management and follow-up is important throughout.
Epigenetic modulation: Research progress on histone acetylation levels in major depressive disorders
Published in Journal of Drug Targeting, 2023
Yuan Meng, Juan Du, Ning Liu, Yuanyuan Qiang, Lifei Xiao, Xiaobing Lan, Lin Ma, Jiamei Yang, Jianqiang Yu, Guangyuan Lu
Current depression treatments mainly involve psychological, physical, and drug therapies [5], among which drug therapy is the first choice for major depressive disorder. Monoamine deficiency is an important factor in the pathogenesis of depression [6], and the currently available therapeutic antidepressant drugs are mainly designed to target the serotonergic and/or noradrenergic systems in the brain [7], with selective serotonin reuptake inhibitors being the most widely used. Blocking norepinephrine and serotonin reuptake in the brain boosts the concentration of transmitters at the receptor site and decreases the reuptake of norepinephrine and serotonin by the presynaptic membrane of nerve terminals. Tricyclic antidepressants are one of the first-choice treatments for depression; however, they have important shortcomings, such as a low effective rate, considerable side effects, slow action onset, and easy recurrence after drug withdrawal. Therefore, it is crucial to develop new therapeutic targets based on an understanding of their pathophysiological mechanisms.
Developments in treating the nonmotor symptoms of stroke
Published in Expert Review of Neurotherapeutics, 2020
Treatment depends on the cause. Treatment of pain caused by spasticity can be treated by reducing spasticity (e.g. with baclofen 5–20 mg four times daily), tizanidine (2–6 mg up to four times daily), botulinum injections every 3 months, massage, strapping, slings, or other physical and occupational therapy interventions [90]. Common side effects of medications for spasticity include weakness, fatigue, headache, and nausea. Intrathecal baclofen may be more effective that oral antispasmodic medications [91]. Other interventions for post-stroke pain include the minimization of glenohumeral subluxation, nerve blocks, and electrical stimulation [90]. Shoulder-hand syndrome is generally treated with physical and occupational therapy, although acupuncture has been used as an adjunct [92]. Treatment of Dejerine–Roussy syndrome is very difficult, but is sometimes ameliorated by stereotactic thalamotomy, deep brain stimulation, or less completely with tricyclic antidepressants, gabapentin, pregabalin, or duloxetine. These last four medications are used to treat a variety of neuropathic pain symptoms. However, effectiveness and side effects increase with the dose. Common side effects of tricyclic antidepressants are discussed in Section 1.1. Common side effects of gabapentin and pregabalin include tingling, sedation, and lower extremity edema. Common side effects of duloxetine include light-headedness, visual changes, eye pain, swelling, or redness, and easy bruising.
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