Despite multiple studies evaluating various therapeutic agents, few have emerged as superior agents for the management of alcohol use disorders. As a result, off-label agents, including gabapentin, are being utilized more frequently in clinical practice. Gabapentin has gained popularity as one of the more commonly studied off-label agents. Gabapentin's relatively low abuse potential, side effect profile, and limited hepatic metabolism make it an attractive option compared with benzodiazepines and other anticonvulsants. Several randomized, placebo- and active-controlled trials have evaluated off-label use of gabapentin for the treatment of alcohol detoxification and dependence. Study results and interpretation from the more robust available data are summarized within this article.Abstract
The use of thyroid hormones to enhance the effects of antidepressants is based on evidence supporting a link between thyroid function and Major Depressive Disorder. Thyroid abnormalities have been found in patients with Major Depressive Disorder and have been correlated with depression severity. Symptoms associated with clinical hypothyroidism include mood disturbances, primarily depression. In addition, an increase in antidepressant treatment resistance has been associated with thyroid abnormalities. This article reviews the existing data regarding triiodothyronine (T3) supplementation of antidepressants in the treatment of major depressive disorder. Medline and EMBASE were searched from 1996 to November 2014 using the key terms triiodothyronine, T3, and treatment-resistant depression. T3 may increase serotonergic neurotransmission and has been studied as an add-on agent in patients with unipolar depression with and without thyroid dysfunction to accelerate, enhance, and augment the effects of tricyclic antidepressants and selective serotonin reuptake inhibitors. Data support the use of T3 augmentation (25-50 μg/d) for the treatment of depressive symptoms in some patient populations without thyroid hormone abnormalities who do not respond to an adequate trial of a tricyclic antidepressant or a selective serotonin reuptake inhibitor. Monitoring for adverse effects and conditions that may be exacerbated by T3 augmentation is recommended.Abstract
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Some of the most bothersome symptoms associated with menopause are the vasomotor symptoms (VMS), characterized by transient elevations in body temperature associated with a narrowing of the thermoneutral zone and an abnormal firing rate of thermosensitive neurons in the hypothalamus. These VMS have traditionally been treated with hormone replacement therapy (HRT); however, after a trial suggesting an association between HRT and a number of serious adverse events, alternative therapies for VMS are being studied. The purpose of this review is to evaluate the available literature regarding the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) for the alleviation of VMS associated with menopause. PubMed and Ovid/MEDLINE keyword searches were conducted. Literature was reviewed for inclusion if it included any SSRI or SNRI for menopausal symptoms published prior to August 31, 2014. Seven studies were included in this review article. No articles were found directly comparing HRT to either SSRIs or SNRIs. Multiple agents within these two classes have been studied for VMS in menopausal and postmenopausal women. Vasomotor symptoms related to the perimenopausal and postmenopausal period can lead to significant physical distress, often requiring medical intervention. Traditional therapies for VMS of menopause have been dominated by the use of HRT. There are conflicting data regarding the use of SSRIs and SNRIs for patients with vasomotor symptoms related to menopause, and these agents may not be ideal for all patients. These agents may be considered as an alternative in patients who have a contraindication or are concerned about using hormonal therapies.Abstract
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Currently, mirtazapine is only approved for use in patients with major depressive disorder, yet the unique dual mechanism of action for this agent has led many to inquire about potential alternative uses. The purpose of this article is to review the evidence available and evaluate the efficacy and tolerability of mirtazapine for use in patients presenting with various forms of anxiety. A search of the medical literature using Ovid Medline and the search terms “mirtazapine” and “anxiety disorders” resulted in the identification of 12 trials and 1 meta-analysis investigating off-label mirtazapine use in various subsets of anxiety. Upon review of the literature, mirtazapine was found to perform significantly better than placebo at controlling symptoms of anxiety with comorbid depression, post-traumatic stress disorder, generalized anxiety disorder, panic disorder, and social anxiety disorder; and with comparable efficacy, in some cases with significantly better response rates, to more current standard treatments such as tricyclic antidepressants and selective serotonin reuptake inhibitors. The observed efficacy of mirtazapine in these trials for the various forms of anxiety and the relatively small side-effect profile warrant consideration for further research into this alternative indication as another option for the treatment of symptoms of anxiety.Abstract
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Depression is a burdening disease state where up to 30% of individuals do not respond to first-line treatment. Adjunctive use of psychostimulants has been investigated for the treatment of depression in patient populations, including those with treatment-resistant depression or terminal illness. The purpose of this paper is to present a review of the literature on the efficacy of using methylphenidate to manage depression. A search was conducted in PubMed, Ovid/MEDLINE, and PsychINFO using the following key words: psychostimulants, stimulants, methylphenidate, alternative therapy, depression, and major depressive disorder. All reports included were published before June 30, 2015. For this review 10 reports, including randomized controlled, case series, and retrospective chart review studies, were identified and assessed. Patient populations studied included patients with treatment-resistant depression, patients with terminal illness, geriatric patients, and patients with miscellaneous indications, such as history of stroke and human immunodeficiency virus (HIV), or acquired immune deficiency syndrome (AIDS). For treatment-resistant depression, treatment differences for fatigue and apathy in favor of methylphenidate were found, but no difference was found for response rates in depression. Additionally, in palliative care and hospice patients, methylphenidate was found to improve fatigue and depressive symptoms. Patients with other conditions (poststroke and HIV patients) achieved some relief of depressive symptoms. The efficacy data for methylphenidate in depression are limited, with inconsistent results in specific patient populations that limit external validity. At this time, it should not be recommended as first-line treatment in depression. Future research should be developed focusing on long-term safety and efficacy in nonspecialized patient populations.Abstract
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Duloxetine, a serotonin-norepinephrine reuptake inhibitor, has been used successfully for adults for the management of neuropathic pain syndromes. Pediatric data are needed because inadequate neuropathic pain management in children and adolescents results in lower psychosocial functioning, delayed development, and decreased quality of life. We aim to describe a case series on the use of duloxetine for the management of symptoms associated with chronic neuropathic pain syndromes in a pediatric population. Data were collected in a naturalistic, consecutive, case report format, from a pediatric pain management clinic for children prescribed duloxetine for analgesia for a variety of neuropathic-type pain conditions. Follow-up data, including self-report of pain, and type and frequency of adverse reactions, were collected to describe the efficacy and safety of duloxetine. Duloxetine was prescribed for the management of self-reported average pain scores of greater than 5 out of 10 on the Faces Pain Scale–Revised for pain that was resistant to other medications. Each of these patients had comorbid psychiatric diagnoses. Reduction in pain following duloxetine therapy was not universal, and all patients discontinued duloxetine therapy prematurely because of adverse effects. Further evidence is needed to demonstrate the efficacy and safety of duloxetine for use in pediatric populations with neuropathic components to their pain. Based on our experience, we suggest considering its use only after failure of other agents. The best management of a pediatric patient's pain condition is likely accomplished through a combination of pharmacotherapy and nonpharmacotherapy interventions.Abstract
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This article will review the pharmacologic and clinical evidence supporting the use of selective norepinephrine reuptake inhibitors, most notably atomoxetine, for the treatment of neuropathic pain states. Many medications initially marketed for psychiatric indications have gained widespread use for their analgesic properties after additional research. In search of alternative treatments for neuropathic pain, current guidelines, published reviews, and primary literature, including both rodent and human trials, were reviewed. The first group of medications to gain widespread use in pain management was the tricyclic antidepressants. As further research was completed and serotonin norepinephrine reuptake inhibitors began to be utilized for their analgesic properties, a growing body of evidence began to indicate that the analgesic properties of these medications were primarily due to the blockade of norepinephrine reuptake with serotonin playing only a minimal role.Abstract
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Peripheral neuropathy is a painful condition that can lead to a reduction in quality of life. The pain, which stems from damaged, hyperexcitable neurons, does not respond to traditional analgesics. However, due to the underlying mechanism of pain, some antidepressants are effective in managing peripheral neuropathy. The purpose of this review is to evaluate the available literature on serotonin-norepinephrine reuptake inhibitors for the management of peripheral neuropathy and outline clinical considerations for choosing an agent. PubMed, Ovid/MEDLINE, and Scopus queries were conducted for relevant literature. Search types were limited to keyword searches and articles were limited to those published prior to March 31, 2015. There were 19 randomized controlled trials included in this review. No articles were found investigating the use of desvenlafaxine, milnacipran, or levomilnacipran for treatment of neuropathy. Both duloxetine and venlafaxine improved pain severity scores for patients suffering from painful peripheral neuropathy compared to placebo. Duloxetine and venlafaxine are able to decrease the severity of peripheral neuropathic pain. None of the trials found that either one of the therapies was able to completely eliminate pain for the patients, which should be an important counseling point for patients to understand. Additionally, patient-specific factors should be considered when choosing an agent, including comorbid disease states and potentially interacting medications.Abstract
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