Antidepressant drugs can be advantageous in treating psychiatric and non-psychiatric illnesses, including spinal disorders. However, spine surgeons remain unfamiliar with the advantages and disadvantages of the use of antidepressant drugs as a part of the medical management of diseases of the spine. Our review article describes a systematic method using the PubMed/Medline database with a specific set of keywords to identify such benefits and drawbacks based on 17 original relevant articles published between January 2000 and February 2018; this provides the community of spine surgeons with available cumulative evidence contained within two tables illustrating both observational (10 studies; three cross-sectional, three case-control, and four cohort studies) and interventional (seven randomized clinical trials) studies. While tricyclic antidepressants (e.g., amitriptyline) and duloxetine can be effective in the treatment of neuropathic pain caused by root compression, venlafaxine may be more appropriate for patients with spinal cord injury presenting with depression and/or nociceptive pain. Despite the potential associated consequences of a prolonged hospital stay, higher cost, and controversial reports regarding the lowering of bone mineral density in the elderly, antidepressants may improve patient satisfaction and quality of life following surgery, and reduce postoperative pain and risk of delirium. The preoperative treatment of preexisting psychiatric diseases, such as anxiety and depression, can improve outcomes for patients with spinal cord injury-related disabilities; however, a preoperative platelet function assay is advocated prior to major spine surgical procedures to protect against significant intraoperative blood loss, as serotonergic antidepressants (e.g., selective serotonin reuptake inhibitors) and bupropion can increase the likelihood of bleeding intraoperatively due to drug-induced platelet dysfunction. This comprehensive review of this evolving topic can assist spine surgeons in better understanding the benefits and risks of antidepressant drugs to optimize outcomes and avoid potential hazards in a spine surgical setting.
Aged ; Antidepressive Agents ; Antidepressive Agents, Tricyclic ; Anxiety ; Blood Platelets ; Bone Density ; Bupropion ; Case-Control Studies ; Cohort Studies ; Delirium ; Depression ; Duloxetine Hydrochloride ; Hemorrhage ; Humans ; Length of Stay ; Methods ; Neuralgia ; Nociceptive Pain ; Pain, Postoperative ; Patient Satisfaction ; Quality of Life ; Risk Assessment ; Serotonin ; Spinal Cord ; Spinal Cord Injuries ; Spine ; Surgeons ; Venlafaxine Hydrochloride

OBJECTIVE: To explore the effectiveness and safety of the combined treatment with acupuncture and venlafaxine hydrochloride on depression in terms of the microstructure change of white matter fiber tracts of brain based on diffusion tensor imaging technology (DTI). METHODS: The prospective study design was adopted. All of 60 patients with depression were randomized into an acupuncture-medication group and a medication group, 30 cases in each one. In the medication group, venlafaxine hydrochloride was used, 75 mg per day in the 1st week, 150 mg per day in the 2nd week and 225 mg per day from the 3rd to 6th week. In the acupuncture-medication group, on the base of the treatment in the medication group, acupuncture was combined. Baihui (GV 20) and Yintang (GV 29) were the main acupoints. The supplementary acupoints were selected according to the clinical symptoms of individuals. The needles were retained for 30 min. Acupuncture was provided once every 2 days, 3 times a week. The consecutive 12 weeks of treatment were required in the two groups. Additionally, a normal group was prepared with 30 healthy volunteers. Separately, before treatment, in 2, 8 and 12 weeks of treatment, Hamilton's depression scale (HAMD-17), Beck depression inventory scale (BDI) and the antidepressant side effect scale (SERS) were adopted to evaluate the effectiveness and safety of the two groups. Moreover, before and after 12 weeks of treatment, DTI was adopted to detect the fractional anisotropy score (FA) of each brain region in the patients. RESULTS: After treatment, the scores of HAMD-17 and BDI were all reduced in the two groups (<0.05). In 8 and 12 weeks of treatment, the scores of HAMD-17 and BDI in the acupuncture-medication group were less than those in the medication group (<0.05). The difference in SERS score was not significant statistically between the two groups (>0.05). Compared with the healthy volunteers, FA scores in 6 brain regions changed obviously in the patients with depression, including the white matter of bilateral frontal lobes, splenium of corpus callosum, left cingulated gyrus, white matter of bilateral inferior temporal gyrus, white matter of bilateral inferior parietal lobe and white matter of bilateral deep temporal occipital region separately. Before treatment, the differences in FA scores of these 6 brain regions were not significant statistically between the two groups (>0.05). After treatment, FA scores in the white matter of bilateral frontal lobes, white matter of bilateral inferior temporal gyrus and white matter of bilateral deep temporal occipital region in the acupuncture-medication group were all higher than those in the medication group (<0.05). CONCLUSION Acupuncture repairs the brain white matter fiber tracts in some brain regions to certain extent and the therapeutic effects are enhanced with the adjuvant medication of venlafaxine hydrochloride.
Acupuncture Therapy ; Brain ; Depression ; therapy ; Diffusion Tensor Imaging ; Humans ; Prospective Studies ; Venlafaxine Hydrochloride

BACKGROUND: Use of antidepressant medications has been linked to detrimental impacts on bone mineral density and osteoporosis; however, the cellular basis behind these observations remains poorly understood. The effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. In this study, we hypothesized that antidepressants have a class- and dose-dependent effect on mesenchymal stem cell (MSC) differentiation, which may affect bone metabolism. METHODS: Human MSCs (hMSCs) were committed to differentiate when either adipogenic or osteogenic media was added, supplemented with five increasing concentrations of amitriptyline (0.001–10 µM), venlafaxine (0.01–25 µM), or fluoxetine (0.001–10 µM). Alizarin red staining (mineralization), alkaline phosphatase (osteoblastogenesis), and oil red O (adipogenesis) assays were performed at timed intervals. In addition, cell viability was assessed using a MTT. RESULTS: We found that fluoxetine had a significant inhibitory effect on mineralization. Furthermore, adipogenic differentiation of hMSC was affected by the addition of amitriptyline, venlafaxine, and fluoxetine to the media. Finally, none of the tested medications significantly affected cell survival. CONCLUSIONS: This study showed a divergent effect of three antidepressants on hMSC differentiation, which appears to be independent of class and dose. As fluoxetine and amitriptyline, but not venlafaxine, affected both osteoblastogenesis and adipogenesis, this inhibitory effect could be associated to the high affinity of fluoxetine to the serotonin transporter system.
Adipogenesis ; Alkaline Phosphatase ; Amitriptyline ; Antidepressive Agents ; Bone Density ; Cell Survival ; Fluoxetine ; Humans ; Mesenchymal Stromal Cells ; Metabolism ; Miners ; Osteoblasts ; Osteoporosis ; Serotonin Plasma Membrane Transport Proteins ; Venlafaxine Hydrochloride

OBJECTIVE: The aim of the present study was to provide clinical consensus and evidence regarding initial treatment strategies for the pharmacological treatment of social anxiety disorder (SAD) in Korea. METHODS: We prepared a questionnaire to derive a consensus from clinicians regarding their preference for the pharmacological treatment of SAD in Korea. Data regarding medication regimens and psychotropic drugs used during initial treatment, the doses used, and the pharmacological treatment duration were obtained. Responses were obtained from 66 SAD experts, and their opinions were classified into three categories (first-line, second-line, third-line) using a chi-square analysis. RESULTS: Clinicians agreed upon first-line regimens for SAD involving monotherapy with selective serotonin reuptake inhibitors (SSRIs) or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine, or combined therapy using antidepressants with betablockers or benzodiazepines on a standing or as-needed basis. First-line psychotropic drug choices for initial treatment included the following: escitalopram, paroxetine, sertraline, venlafaxine, and propranolol. The medication dosage used by domestic clinicians was found to be comparable with foreign guidelines. Domestic clinicians tended to make treatment decisions in a shorter amount of time and preferred a similar duration of maintenance treatment for SAD when compared with foreign clinicians. CONCLUSION: This study may provide significant information for developing SAD pharmacotherapy guidelines in Korea, especially in the early stage of treatment.
Antidepressive Agents ; Anxiety Disorders ; Anxiety ; Benzodiazepines ; Citalopram ; Consensus ; Drug Therapy ; Korea ; Paroxetine ; Propranolol ; Psychotropic Drugs ; Serotonin Uptake Inhibitors ; Sertraline ; Venlafaxine Hydrochloride

Acute Disease ; Antidepressive Agents, Second-Generation ; adverse effects ; Glaucoma, Angle-Closure ; chemically induced ; Humans ; Intraocular Pressure ; Venlafaxine Hydrochloride ; adverse effects

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of escitalopram, paroxetine and venlafaxine in Korean patients with major depressive disorder (MDD). METHODS: A total of 449 Korean MDD patients were recruited in a six-week, randomized, rater-blinded, active-controlled trial and were evenly randomized to paroxetine, venlafaxine, or escitalopram treatment. RESULTS: When comparing the mean difference for the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HDRS) total scores during six weeks, paroxetine (−6.4±0.4, and −5.4±0.4, respectively) was found to be significantly superior to escitalopram (−3.7±0.5 and −3.1±0.4, respectively). Venlafaxine had a significantly lower MADRS total score (−5.4±0.4) than escitalopram. When adjusting baseline variables, the response, according to the MADRS and HDRS scores, in the paroxetine group was greater than that for the escitalopram group (odds ratio [OR]=2.43, 95% confidence interval [CI]=1.42–4.16 for MADRS; and OR=2.32, 95% CI=1.35–3.97 for HDRS) and the venlafaxine group (OR=1.94, 95% CI=1.17–3.21 for MADRS; and OR=1.71, 95% CI=1.03–2.83 for HDRS). Despite that the overall tolerability was high and similar among the three groups, a total of 268 subjects (59.7%) prematurely discontinued treatment, representing the main limitation of the present study. CONCLUSION: Although a low study completion rate limits generalizability, our findings suggest that paroxetine might be superior to escitalopram in Korean MDD patients. Further studies should be conducted to draw a definite conclusion.
Citalopram* ; Depression ; Depressive Disorder, Major* ; Humans ; Paroxetine* ; Venlafaxine Hydrochloride*

The serotonin syndrome is a serioius medical condition due due to an intensive stimulation of setonin receptors. It is a rare, but severe, consequence of interaction between serotomimetic agents. This is a report of a 70-year-old woman steadily in therapy with venlafaxine and rizatriptan for migraine and major depressive syndrome. She was admitted to neurology unit for decreased light reflex with miotic pupils, global hyperreflexia, tremor, anxiety, ataxia and incoordination. The patient was diagnosed as a probable case of serotonin syndrome due to a pharmacological interaction between venlafaxine and rizatriptan trigged by opioid intake. In this paper, the development of syntomatology, the clinical examination and the possible pharmacokinetics explanation were carefully discussed and analysed.
Aged ; Anxiety ; Ataxia ; Codeine* ; Depressive Disorder ; Depressive Disorder, Major ; Female ; Humans ; Migraine Disorders ; Neurology ; Pharmacokinetics ; Prescription Drug Misuse ; Pupil ; Reflex ; Reflex, Abnormal ; Serotonin Syndrome* ; Serotonin* ; Tremor ; Venlafaxine Hydrochloride

PURPOSE: In this study, we investigated overactive bladder (OAB) functions in male patients who used antidepressant drugs (ADs) that were previously examined in female patients, based on conflicting data in literature regarding the effects of AD on OAB and the differences between male and female urinary system physiologies (anatomical and hormonal). METHODS: The study included 202 male patients (a control group of 90 healthy subjects, and an experimental group of 112 patients taking ADs for different disorders). All the patients completed the overactive bladder-validated 8 (OAB-V8) questionnaire, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and the Beck Depression Inventory (BDS). RESULTS: The OAB-V8, ICIQ-SF, and BDS scores for the antidepressant users were significantly higher than those of the control group. The highest prevalence of OAB symptoms was observed in patients taking venlafaxine (68.2%), and the lowest prevalence was in patients taking sertraline (28.0%). Moreover, the frequency of OAB between the antidepressant groups was statistically significant. The univariate logistic regression analyses showed a significant relationship between the presence of OAB, antidepressant usage, BDS score, and the age of a patient. In the multivariate logistic regression analyses, the association between the presence of OAB and antidepressant usage was statistically significant. CONCLUSIONS: The present study showed that the incidence of OAB and the severity of OAB symptoms increased in males using antidepressants for various disorders. This may have been due to unique pharmacological effects, on a molecular or individual level, of serotonin-norepinephrine reuptake inhibitors.
Antidepressive Agents ; Depression ; Female ; Healthy Volunteers ; Humans ; Incidence ; Logistic Models ; Male* ; Prevalence ; Prospective Studies* ; Sertraline ; Urinary Bladder, Overactive* ; Venlafaxine Hydrochloride

Venlafaxine is a serotonergic and noradrenergic reuptake inhibitor which is used for the treatment of depression. We report a case of galactorrhea in a patient with major depressive disorder after starting treatment with venlafaxine. In particular, we discuss the course of hyper and normoprolactinemic galactorrhea. We managed this side effect initially by dose reduction and further by switching to essitalopram. Physicians should be aware of endocrinologic side effects such as galactorrhea during the serotonin and noradrenaline reuptake inhibitor treatment.
Depression ; Depressive Disorder, Major ; Female ; Galactorrhea* ; Humans ; Norepinephrine ; Pregnancy ; Prolactin ; Serotonin ; Venlafaxine Hydrochloride*

OBJECTIVE: The multidrug resistance 1 (ABCB1, MDR1) gene, encoding P-glycoprotein, is extensively distributed and expressed in various tissues, such as a blood-brain barrier transporter. P-glycoprotein plays an important role in controlling the passage of substances between the blood and brain. The current study aimed to investigate possible associations of functional ABCB1 polymorphisms (C3435T, G2677T and C1236T) with response to antidepressant treatment and serum cortisol levels in Taiwanese patients with major depressive disorder (MDD). METHODS: We recruited 112 MDD patients who were randomized to fluoxetine (n=58, mean dose: 21.4+/-4.5 mg/day) or venlafaxine (n=54, 80.2+/-34.7 mg/day) treatment for 6 weeks. The 21-item Hamilton Depression Rating Scale (HDRS) was administered initially and biweekly after treatment, and cortisol levels were assessed initially and after 6-week antidepressant treatment. RESULTS: The initial HDRS scores and the HDRS scores after six weeks of antidepressant treatment were not significantly different among the different genotypes in each polymorphism of ABCB1. The percentage changes of HDRS scores over time were significantly different in the polymorphisms of ABCB1 G2677T (p=0.002). MDD patients with the G/G genotype of ABCB1 G2677T had a worse antidepressant treatment response. However, the polymorphisms of ABCB1 genotypes were not significantly associated with cortisol levels before and after antidepressant treatment in MDD patients. CONCLUSION: The results suggested that the variants of ABCB1 may influence the short-term antidepressant response in MDD patients. Further details of the underlying mechanisms of ABCB1 in antidepressant treatment remain to be clarified.
Antidepressive Agents ; Blood-Brain Barrier ; Brain ; Depression ; Depressive Disorder, Major ; Drug Resistance, Multiple ; Fluoxetine ; Genotype ; Humans ; Hydrocortisone ; P-Glycoprotein ; P-Glycoproteins ; Venlafaxine Hydrochloride