Effects of milnacipran and paroxetine on anxiety state and headache severity of patients with generalized anxiety disorder / 中国医师进修杂志

Objective:To compare the effects of milnacipran and paroxetine on anxiety state and headache severity of patients with generalized anxiety disorder (GAD).Methods:Ninety-six patients with GAD treated in Zaozhuang Mental Health Center from January 2019 to September 2020 were selected and randomly divided into the paroxetine group (treatment with oral paroxetine) and the milnacipran group (treatment with oral milnacipran), each group with 48 cases. A course of treatment consists of 4 weeks. After 3 months of regular medication, the clinical efficacy, Hamilton Anxiety Scale (HAMA) scores, visual analogue scale (VAS) scores, migraine-specific quality of life questionnaire (MSQ V2.1) scores, and Headache Impact Test-6 (HIT-6) scores were compared between the two groups. Adverse reactions during the treatment were recorded in both groups.Results:The total effective rate in the milnacipran group at 4 weeks and 3 months after treatment were significantly higher than those in the paroxetine group: 47.92%(23/48) vs. 22.92%(11/48), χ2 = 6.56, P<0.05; 75.00%(36/48) vs. 51.47%(26/48), χ2 = 4.55, P<0.05. After treatment for 4 weeks and 3 months, the HAMA scores, VAS scores, MSQ V2.1 scores and HIT-6 scores in the milnacipran group were significantly lower than those in the paroxetine group ( P<0.05). The difference of incidence of adverse reactions in the two groups had no statistical significance ( P>0.05). Conclusions:For patients with GAD, the treatment effect of milnacipran is more significant than paroxetine, which can not only reduce patients′ anxiety state and headache degree, but also improve their specific quality of life, with high safety.

Efficacy and tolerability of milnacipran and escitalopram: a comparative study among patients of depression

Background: The present prospective, open labelled study was designed to evaluate the efficacy and tolerability of escitalopram, selective serotonin reuptake inhibitors (SSRI) in comparison with milnacipran, dual serotonin and noradrenaline reuptake inhibitors (SNRI) in the treatment of major depressive disorder.Methods: Outpatients (N=120) with an ongoing/newly diagnosed ICD-10 major depressive episode and having a minimum score of 8 on the 21-item Hamilton Depression Rating Scale (HDRS) were assigned to escitalopram, 10–20 mg/day (54 patients) and milnacipran 50-100mg (66 patients), for an 8 week treatment period with follow up at 2nd, 4th and 8th week. The parameters for efficacy were improvement (decrease in HDRS scores at 8 weeks from baseline values), response (decrease of ?50% in the HDRS scores) and remission (HDRS score of ?7). Tolerability was assessed by comparing the frequency of adverse effects and drop out rate due to the same at the end of 2nd, 4th and 8th week in both the groups.Results: Improvement, Response rate and Remission rates at the end of eight weeks were 71.11%, 83.33% and58.33% for escitalopram and 59.35%, 34.14% and75.6% for milnacipran respectively. Adverse experiences were reported by 14% of patients in escitalopram group and 79.2% patients in milnacipran group at 8 weeks. Additionally, there were significantly lesser dropouts due to adverse events in escitalopram (3.70%) than in milnacipran group (30%).Conclusions: Escitalopram, the Senantiomer of citalopram, is a safe and effective antidepressant with potentially superior tolerability and comparable efficacy to the dual reuptake inhibitor, Milnacipran.

Comparison of the Medication Effects between Milnacipran and Pregabalin in Fibromyalgia Syndrome Using a Functional MRI: a Follow-up Study

PURPOSE: In this study, the medication effects of Milnacipran and Pregabalin, as well known as fibromyalgia treatment medicine, in fibromyalgia syndrome patients were compared through the change of BOLD signal in pain related functional MRI. MATERIALS AND METHODS: Twenty fibromyalgia syndrome patients were enrolled in this study and they were separated into two groups according to the treatment medicine: 10 Milnacipran (MLN) treatment group and 7 Pregabalin (PGB) treatment group. For accurate diagnosis, all patients underwent several clinical tests. Pre-treated and post-treated fMRI image with block-designed pressure-pain stimulation for each group were obtained to conduct the statistical analysis of paired t-test and two sample t-test. All statistical significant level was less than 0.05. RESULTS: In clinical tests, the clinical scores of the two groups were not significantly different at pre-treatment stage. But, PGB treatment group had lower Widespread Pain Index (WPI) and Brief Fatigue Inventory (BFI) score than those of MLN treatment group at post-treatment stage. In functional image analysis, BOLD signal of PGB treatment group was higher BOLD signal at several regions including anterior cingulate and insula than MLN treatment group at post-treatment stage. Also, paired t-test values of the BOLD signal in MLN group decreased in several regions including insula and thalamus as known as 'pain network'. In contrast, size and number of regions in which the BOLD signal decreased in PGB treatment group were smaller than those of MLN treatment group. CONCLUSION: This study showed that MLN group and PGB group have different medication effects. It is not surprising that MLN and PGB have not the same therapeutic effects since these two drugs have different medicinal mechanisms such as antidepressants and anti-seizure medication, respectively, and different detailed target of fibromyalgia syndrome treatment. Therefore, it is difficult to say which medicine will work better in this study.

Evaluation of the Neurological Safety of Epidural Milnacipran in Rats

BACKGROUND: Milnacipran is a balanced serotonin norepinephrine reuptake inhibitor with minimal side effects and broad safety margin. It acts primarily on the descending inhibitory pain pathway in brain and spinal cord. In many animal studies, intrathecal administration of milnacipran is effective in neuropathic pain management. However, there is no study for the neurological safety of milnacipran when it is administered neuraxially. This study examined the neurotoxicity of epidural milnacipran by observing behavioral and sensory-motor changes with histopathological examinations of spinal cords in rats. METHODS: Sixty rats were divided into 3 groups, with each group receiving epidural administration of either 0.3 ml (3 mg) of milnacipran (group M, n = 20), 0.3 ml of 40% alcohol (group A, n = 20), or 0.3 ml of normal saline (group S, n = 20). RESULTS: There were no abnormal changes in the behavioral, sensory-motor, or histopathological findings in all rats of groups M and S over a 3-week observation period, whereas all rats in group A had abnormal changes. CONCLUSIONS: Based on these findings, the direct epidural administration of milnacipran in rats did not present any evidence of neurotoxicity in behavioral, sensory-motor and histopathological evaluations.

Effect of the Combined Use of Tramadol and Milnacipran on Pain Threshold in an Animal Model of Fibromyalgia

BACKGROUND/AIMS: Acidic saline injections produce mechanical hyperresponsiveness in male Sprague-Dawley rats. We investigated the effect of milnacipran in conjunction with tramadol on the pain threshold in an acidic saline animal model of pain. METHODS: The left gastrocnemius muscle of 20 male rats was injected with 100 microL of saline at pH 4.0 under brief isoflurane anesthesia on days 0 and 5. Rats administered acidic saline injections were separated into four study subgroups. After determining the pre-drug pain threshold, rats were injected intraperitoneally with one of the following regimens; saline, milnacipran alone (60 mg/kg), milnacipran (40 mg/kg) plus tramadol (20 mg/kg), or milnacipran (40 mg/kg) plus tramadol (40 mg/kg). Paw withdrawal in response to pressure was measured at 30 min, 120 min, and 5 days after injection. Nociceptive thresholds, expressed in grams, were measured with a Dynamic Plantar Aesthesiometer (Ugo Basile, Italy) by applying increasing pressure to the right or left hind paw until the rat withdrew the paw. RESULTS: A potent antihyperalgesic effect was observed when tramadol and milnacipran were used in combination (injected paw, p=0.001; contralateral paw, p=0.012). This finding was observed only at 30 min after the combination treatment. CONCLUSIONS: We observed potentiation of the antihyperalgesic effect when milnacipran and tramadol were administered in combination in an animal model of fibromyalgia. Further research is required to determine the efficacy of various combination treatments in fibromyalgia in humans.

The Combined Antiallodynic Effect of Gabapentin and Milnacipran in a Rat Neuropathic Pain Model / 대한통증학회지

BACKGROUND: Anticonvulsants and antidepressants are adjuvant analgesic drugs that are used widely for treating chronic neuropathic pain syndromes. The combined analgesic effect of gabapentin and milnacipran was investigated with a rat neuropathic pain model. METHODS: The rat neuropathic pain model was made by ligating the spinal nerves (L5 and L6). An intrathecal catheter was inserted into the subarachnoid space. Tactile allodynia was tested with the up-down method using von Frey hair. We determined the antiallodynic effect of intraperitoneal (I.P.) and intrathecal (I.T.) gabapentin. The combined effect of I.P. gabapentin (50 mg/kg) and milnacipran (0, 10 and 30 mg/kg) was investigated. RESULTS: Intraperitoneal and intrathecal administration of gabapentin increased the threshold for tactile allodynia (the ED50 was 60.6 mg/kg and 45.5microng, respectively). Co-administration of I.P. milnacipran increased the antiallodynic effect of I.P. gabapentin in a dose-dependent fashion. CONCLUSION: The combined administration of milnacipran and gabapentin may increase the total analgesic effect during treatment of neuropathic pain.

The Effects of Milnacipran on Rat Pain Model / 대한마취과학회지

BACKGROUND: Serotonin and norepinephrine are known as agents of the nonopiate endogenous descending pain control system. Recently, selective serotonin norepinephrine receptor inhibitors (SNRIs) have been developed as antidepressants. We studied the effects of milnacipran, a SNRI in a spinal nerve ligation (SNL) model and formalin test. METHODS: Male Sprague-Dawley rats weighing 200-250 gm were used for this study. In the SNL model, under an anesthetic state, the 5th lumbar spinal nerve was ligated and a PE-10 catheter was inserted into the subarachnoid space. Milnacipran was injected intraperitoneally or intrathecally and the threshold of tactile allodynia was measured. In the formalin test, milnacipran was administered intraperitoneally or intrathecally. 30 minutes after intraperitoneal injection or 60 minutes after intrathecal injection the formalin test was performed and flinching was counted for 60 minutes. RESULTS: In the spinal nerve ligation model, pain response decreased significantly (P <0.05). But, after intraperitoneal milnacipran administration in the spinal nerve ligation model, no difference in mechanical allodynia was observed between among groups. In formalin test, intraperitoneal and intrathecal milnacipran administration decreased phase I response, but there was no change in phase II response. CONCLUSIONS: Milnacipran reduced neuropathic pain after intrathecal administration. But there was no difference after intraperitoneal administration. Intraperitoneal and intrathecal milnacipran administration in formalin test reduced only the acute phase, but no difference in chronic chemical induced centralization pain was observed.

The Efficacy and Safety of Milnacipran in Patients with Major Depression: A comparison with Fluoxetine / 신경정신의학

OBJECTIVES: This 6-week, open label randomized, multicenter study was conducted to evaluate the antidepressant effect and safety of milnacipran and fluoxetine in patients with major depression. METHODS: The study was done in patients with major depression diagnosed by DSM-IV who score > or =17 in 17 items Hamilton Rating Scale for Depression (17-item HAM-D) and score > or =25 in Montgomery and Asberg Depression Rating Scale (MADRS). A total of 87 patients were randomized to milnacipran group and fluoxetine group. In cases of the patients taking other antidepressants, 6 weeks of each medication was administered after 7 days of drug excretion period. The evaluation was done using 17 item HAM-D, MADRS, Clinical Global Impression Scale (CGI), and COVI scale after baseline, 1 week, 2 weeks, 4 weeks, and 6 weeks. The side effects that had occurred during the period of our study were put in records by developed/disappeared time, severities, incidences, managements and results. RESULTS: A total of 87 patients were enrolled. 70 (milnacipran group 39;fluoxetine group 31) of them were included for the 6 weeks of research and 17 of them dropped out within the first week, not due to adverse reactions or deficiency of effects. Total 17 item HAM-D scores, total points of MADRS, and CGI showed significant decrease after 1 week in each treatment group and continued decrease after 2 weeks and 4, 6 weeks. But there was no difference between milnacipran group and fluoxetine group in the antidepressant effect. There were no significant changes in vital sign, CBC, chemistry, and EKG in each treatment group. The commonly reported side effects of minlacipran were nausea (25.0%), headache (10.7%), vomiting (7.1%), constipation (7.1%), dizziness (7.1%) and those of fluoxetine were GI trouble (11.1%), diarrhea (11.1%), insomnia (11.1%), agitation (5.6%), and dizziness (5.6%). CONCLUSION: Milnacipran was effective for the improvement of depressive symptoms and was well tolerated and safe in patients with depression.

Milnacipran versus Sertraline in Major Depressive Disorder: A Double-Blind Randomized Comparative Study on the Treatment Effect and cbeta-Adrenergic Receptor Responsiveness / 대한정신약물학회지

OBJECTIVE: This study was aimed to compare the efficacy and tolerability of milnacipran and sertraline treatment in patients with major depressive disorder and to evaluate the relationships between beta-adrenergic receptor responsiveness and depressive mood states. METHODS: Fifty three patients who had a diagnosis of major depressive disorder according to the DSM-IV and showed scores of 17 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomly assigned to either milnacipran or sertraline treatment group. Each patient received 8 weeks of antidepressant treatment with one of the two drugs. Efficacy was assessed using the HAM-D, Beck Depression Inventory (BDI), Montgomery and Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI). Twenty normal control subjects who had no history of psychiatric and major medical illness and were matched with the depressed patients considering age, sex and body mass index were recruited for the comparison of beta-adrenergic receptor responsiveness between depressed patients and normal control subjects. We measured beta-adrenergic receptor density, lymphocyte cAMP ratio (ratio of isoproterenol-stimulated cAMP/basal cAMP), and receptor affinity (Kd) in all subjects. We also investigated beta-adrenergic receptor responsiveness before and after treatment in depressed patients. RESULTS: Twelve patients in milnacipran group and 15 patients in sertraline group were completed this study. In all assessment scales for depression, we found significant decrease in depression severity in both milnacipran and sertraline groups. Both of the two drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period. And there were significant differences in the means of Kd values between control subjects and depressed patients before treatment. We found a significant negative correlation between Kd values and BDI scores. After treatment with either milnacipran or sertraline, cAMP ratio (4.8+/-1.6 vs 5.7+/-2.5, p=0.095) and Kd value (65.6+/-11.9 vs 74.6+/-7.8, p=0.066) tended to increase, but there was no significant difference in beta-adrenergic receptor responsiveness between milnacipran and sertraline group. CONCLUSION: Both milnacipran and sertraline were not different in the clinical efficacy in major depressive disorder. In depressed patients, beta-adrenergic receptor responsiveness is reduced and both milnacipran and sertraline antidepressants tended to increase beta-adrenergic receptor responsiveness.