International Journal of Psychiatry in Clinical Practice, 2010; 14: 68–71
SHORT REPORT
Efficacy of milnacipran in the treatment of chronic pain syndromes MITSUHIRO KAMATA1, SHINGO NAITO2, HISASHI HIGUCHI3, AKIHITO SUZUKI4 & KOICHI OTANI4 Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Victoria on 12/16/14 For personal use only.
1Health Administration
Center, Yamagata University, Kojirakawa-machi, Yamagata, Japan, 2Department of Psychiatry, Akita City Hospital, Akita City, Akita, Japan, 3Department of Psychiatry, St. Marianna University School of Medicine, Kawasaki City, Kanagawa, Japan, and 4Department of Psychiatry,Yamagata University School of Medicine,Yamagata City,Yamagata, Japan
Abstract Eleven outpatients with chronic pain syndromes other than fibromyalgia were treated for 12 weeks with milnacipran, a novel serotonin noradrenaline reuptake inhibitor. The agent was administered at 50–150 mg/day, and the mean ⫾ SD dose at 12 weeks or at the time drug treatment was stopped was 84.1 ⫾ 32.2 mg/day. None of the patients met the DSM-IV criteria for a major depressive disorder. Abdominal, chest, back, arm, leg or glossal pain, or headache was involved. Pain was assessed clinically by means of a visual analog scale (VAS) before and 12 weeks after the start of milnacipran treatment, or at the time drug treatment was stopped. The mean ⫾ SD decrease in VAS scores was 42.3 ⫾ 31.6 (50.8 ⫾ 49.2%). One patient discontinued treatment after 4 weeks because of nausea, whereas others tolerated the agent well. These results suggest that the use of milnacipran in patients with a variety of chronic pain syndromes is beneficial. Key Words: Milnacipran, SNRI, antidepressant, chronic pain
Introduction Tricyclic antidepressants (TCAs) have long been considered the standard treatment for a variety of chronic pain syndromes [1–5]. Chronic pain is defined as pain that persists for longer than 3 months [1,6]. The effects of TCAs on both norepinephrine (NE) and serotonin (5-HT) are important because these neurotransmitters are thought to be involved in the pathogenesis of chronic pain syndromes [1,2,5]. Antidepressants have an effect on chronic pain syndromes independent of any effects on mood [1,7,8]. Despite the putative efficacy of TCAs in the treatment of chronic pain, their use has been compromised by the high degree of poorly tolerated adverse effects [1–5]. Newer antidepressants, which are non-TCAs with higher tolerance, have been studied for the treatment of chronic pain [2–4]. With regard to the analgesic effects to treat chronic pain, however, TCAs are more effective than noradrenaline reuptake inhibitor (NRIs), which are more effective than selective serotonin reuptake inhibitors (SSRIs) [9]. Therefore, it has been suggested that the ideal antidepressant agent for management of chronic pain would modulate both NE and 5-HT but lack the nontherapeutic synaptic effects associated with
TCAs or heterocyclic antidepressants [2]. A number of studies have documented the efficacy of serotonin norepinephrine reuptake inhibitors (SNRIs) in the treatment of chronic pain [1–3,5,10,11]. Milnacipran is a novel SNRI that is similar to imipramine, a TCA, with respect to both selectivity and absolute affinity [12]. However, this agent does not interact with post-synaptic receptors, giving it a favorable tolerance profile [13]. The efficacy of milnacipran in relieving pain has been documented in various types of chronic pain syndrome, including fibromyalgia [5]. We recently reported a case series describing the effects of milnacipran on various chronic pain syndromes, including abdominal pain, back pain, glossal pain, chest pain and headache [14]. Here, we present results from an open clinical trial, designed to quantify the efficacy of milnacipran to treat chronic pain syndromes other than fibromyalgia in more subjects than in our previous report [14]. Patients and methods Patients Eleven outpatients (two men, nine women) suffering from various types of chronic pain syndrome for at
Correspondence: Mitsuhiro Kamata. Tel: +81 23 628 4152. Fax: +81 23 628 4152. E-mail: [email protected] (Received 24 March 2009; accepted 24 August 2009) ISSN 1365-1501 print/ISSN 1471-1788 online © 2010 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS) DOI: 10.3109/13651500903282865
None None
Paroxetine 20 mg Fluvoxamine 75 mg None None None Paroxetine 20 mg Paroxetine 20 mg
None Paroxetine 30 mg
84.1 ⫾ 32.2
100 50
100 150 50 100 100 50 100
Etizolam 1 mg Alprazolam 1.2 mg, triazolam 0.25 mg, zolpidem 10 mg Brotizolam 0.25 mg Alprazolam 0.8 mg Zolpidem 10 mg Brotizolam 0.25 mg None None Etizolam 1 mg, alprazolam 1.2 mg, zolpidem 10 mg None None 75 50
least 3 months were initially enrolled in the study. Abdominal, chest, back, arm, leg or glossal pain, or headache was involved. Five of these patients were also included in our previous case series [14]. Participants had no evidence of serious or uncontrolled medical illness. Although one patient was being treated for angina pectoris and two patients were being treated for hypertension, their conditions remained stable during the study period. None of the patients met the DSM-IV criteria for a major depressive disorder, and none had depressive symptoms to a clinically significant degree. After presenting a complete description of the study to the patients, written informed consent was obtained. This study received ethics committee approval and was conducted in accordance with the ethical principles derived from the Declaration of Helsinki and the guidelines of the International Conference on Harmonization (ICH)/Good Clinical Practice (GCP). A summary of patient characteristics is outlined in Table I. Patient age was 66.7 ⫾ 17.4 years (mean ⫾ SD), and the duration of pain was 16.3 ⫾ 17.5 months (mean ⫾ SD).
16.3 ⫾ 17.5
Back pain Back pain
Abdominal and chest pain Back pain, headache Glossal pain Glossal pain, back pain Glossal pain Abdominal and back pain Arm, leg pain 4 33 12 15 5 3 60
4 3
Abdominal pain Abdominal pain, headache 16 24
Milnacipran treatment was started at 25 or 50 mg/day and was increased according to clinical response over 12 weeks. Patients suffering from insomnia were given drugs to treat the insomnia. All other medications were kept constant during the study. Only the dosage of milnacipran was changed, if necessary. Milnacipran was administered at 50–150 mg/day by the end of the 12-week period or by the time the drug treatment was stopped, and the dose of this agent at the end of the study was 84.1 ⫾ 32.2 (mean ⫾ SD) mg/day. Before the start of milnacipran treatment, four patients had been treated with paroxetine, and one had been treated with fluvoxamine, both SSRIs. To prevent acute withdrawal symptoms in these patients, a washout period was not used.
Mean ⫾ SD
66.7 ⫾ 17.4
F M 66 77 10 11
F M F F F F F 72 23 63 78 75 74 47 3 4 5 6 7 8 9
F F
Assessment
82 77
Type of pain Sex Age (years) Patient
69
Drug administration
1 2
Concomitant medications (mg/day) Milnacipran dose at end of study (mg/day) Duration of illness (months)
Table I. Patient characteristics and concomitant medications.
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Victoria on 12/16/14 For personal use only.
Previously used antidepressant (mg/day)
Efficacy of milnacipran on choronic pain syndromes
Chronic pain was assessed clinically by means of a visual analog scale (VAS) before and at 12 weeks after the start of milnacipran or at the time the drug treatment was stopped. Such assessments require patients to describe the intensity of their pain by placing a mark on a 100-mm line anchored by “no pain” at 0 mm and “worst imaginable pain” at 100 mm [15]. VAS scores before and at 12 weeks after the start of the milnacipran were compared. The Clinical Global Impressions-Severity of Illness scale (CGI-S) was used to assess the patients’ overall clinical condition [16]. The Clinical Global
70
M. Kamata et al.
Table II. Efficacy of milnacipran in the treatment of chronic pain syndromes. Patient
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Victoria on 12/16/14 For personal use only.
1 2 3 4 5 6 7 8 9 10 11 Mean ⫾ SD
% Change in VAS score
CGI-S score at Baseline
CGI-S score at end of study
CGI-I score at end of study
⫺87 ⫺79 ⫺42 ⫺86 ⫺14 ⫺80 ⫺80 60 ⫺11 ⫺89 ⫺ ⫺50.8 ⫾ 49.2
6 7 7 6 5 4 4 4 7 7 5 5.6 ⫾ 1.3
3 3 4 2 5 2 2 6 7 2 ⫺ 3.6 ⫾ 1.8
1 1 2 1 4 2 2 6 4 1 ⫺ 2.4 ⫾ 1.7
Impressions-Severity of Improvement scale (CGI-I) was also used [16].
Results The mean (⫾SD) VAS and CGI-S scores at baseline were 73.3⫾19.3 and 5.6⫾1.3, respectively. Ten patients continued milnacipran treatment and tolerated the drug well. One male patient withdrew from treatment without explanation, and one female patient stopped taking the drug at 4 weeks after the start of treatment because of nausea; thus, two patients stopped taking milnacipran. The mean (⫾SD) VAS score at endpoint was 30.7⫾27.2, which was a mean decrease (%) of 42.3⫾31.6 (50.8⫾49.2%). Table II shows the % decrease in VAS scores, changes in CGI-S score, and final CGI-I scores. The mean (⫾SD) CGI-S score was 3.6⫾1.8 at the end of the study. Four patients had a final CGI-I score of 1, “very much improved”, and three patients had a final CGI-I score of 2, “improved”. Two patients had a final CGI-I score of 4, “no change”. Chronic pain worsened in one patient after milnacipran treatment, and her VAS score changed from 50 to 80. Her final CGI-I score was 6, “much worse”.
drug. One patient experienced persistent nausea and thus discontinued treatment. Although nausea is the most common adverse effect of treatment with milnacipran [17], the rate of this adverse effect with milnacipran is relatively low compared to that with fluvoxamine [17]. Five patients had been treated with an SSRI before treatment with milnacipran. The daily dose of SSRIs used in these patients was the recommended therapeutic dose in Japan. There was little clinical improvement with SSRI treatment in these patients, but there was mild or marked clinical improvement with the milnacipran treatment. Pharmacological treatment with milnacipran was therefore beneficial for these patients. The present study found the use of milnacipran in patients with various chronic pain syndromes to be beneficial. Taken together with previous reports of the success of milnacipran in treating a wide range of chronic pain syndromes [5,10,14], this drug effectively relieves pain in chronic pain syndromes. Nevertheless, as this study was an open clinical trial without a placebo group, the reported improvements gained by patients who received milnacipran must be interpreted with caution. Furthermore, as the number of subjects was relatively small, the present results should be confirmed in a larger sample.
Discussion The patients in the present study showed a 50.8% decrease in VAS scores with milnacipran treatment, and seven patients showed some improvement in CGI-I score. Thus, these patients benefited from this treatment for chronic pain syndrome. Furthermore, six of the 11 patients were over 70 years of age and they tolerated the milnacipran well, despite their age. Accordingly, these results suggest that milnacipran is beneficial for the treatment of chronic pain in terms of both efficacy and tolerability. However, it should be noted that two patients stopped taking the
Key points • Chronic pain is defined as pain that persists for longer than 3 months • It has been suggested that the ideal antidepressant agent for management of chronic pain modulates both NE and 5-HT, but lacks the nontherapeutic synaptic effects associated with TCAs • Milnacipran, an SNRI, appears to be a useful agent in the treatment of a wide range of chronic pain syndromes
Efficacy of milnacipran on choronic pain syndromes Acknowledgement None. Statement of interest This study did not receive any financial or material support. The authors declare that they have no financial or other relationships relevant to the subject of this article.
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Victoria on 12/16/14 For personal use only.
References [1] Ansari A. The efficacy of newer antidepressants in the treatment of chronic pain: a review of current literature. Harvard Rev Psychiatry 2000;7:257–77. [2] Barkin RL, Fawcett J. The management challenges of chronic pain: The role of antidepressants. Am J Ther 2000;7:31–47. [3] Lynch ME. Antidepressants as analgesics: a review of randomized controlled trials. Pharmacol Pain 2001;26:30–36. [4] Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: An update and effect related to mechanism of drug action. Pain 1999;83:389–400. [5] Briley M. Clinical experience with dual action antidepressants in different chronic pain syndrome. Hum Psychopharmacol 2004;19:S21–5. [6] Bouckoms MB, Hackett TP. Pain patients. In: Cassem NH, editors. Massachusetts General Hospital Handbook of General Hospital Psychiatry. 4th ed. St. Louis, MO: Mosby-Yearbook, 1997:367–413. [7] Max MB. Treatment of post-herpetic neuralgia: antidepressants. Ann Neurol 1994;35(Suppl):S50–3. [8] Onghena P, Houdenhove BV. Antidepressant-induced analgesia in chronic non-malignant pain: A meta-analysis of 39 placebo-controlled studies. Pain 1992;49:205–19.
71
[9] Fishbain DA, Culter R, Rosomoff HL, Rossomoff RS. Evidence-based data from animal and human experimental studies on pain relief with antidepressants: A structured review. Pain Med 2000;1:310–6. [10] Leo RJ, Brooks VL. Clinical potential of milnacipran, a serotonin and norepinephrine inhibitor, in pain. Curr Opin Investig Drugs 2006;7:637–42. [11] Barkin RL, Barkin S. The role of venlafaxine and duloxetine in the treatment of depression with decremental changes in somatic symptoms of pain, chronic pain, and the pharmacokinetics and clinical considerations of duloxetine pharmacotherapy. Am J Ther 2005;12:431–8. [12] Moret C, Charveron M, Finberg JPM, Couzinier JP, Briley M. Biochemical profile of milnacipran (F 2207), 1-phenyl1-diethyl-aminocarbonyl-2-aminoethylcyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology 1985;24:1211–9. [13] Kasper S, Pletan Y, Solles A, Tournoux A. Comparative studies with milnacipran and tricyclic antidepressants in the treatment of patients with major depression: A summary of clinical trial results. Int Clin Psychopharmacol 1996; 11(Suppl 4):35–9. [14] Kamata M, Takahashi H, Naito S, Higuchi H. Effectiveness of milnacipran for the treatment of chronic pain: A case series. Clin Neuropharmacol 2004;27:208–10. [15] De Loach LJ, Higgins MS, Caplan AB, Stiff JL. The Visual Analog Scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesth Analg 1998;86:102–6. [16] Guy W. ECDEU assessment Manual for Psychopharmacology, Revised. US Dept Health, Education, and Welfare publication (ADM) 76–338. Rockville, MD: National Institute of Mental Health 1976. [17] Clerc G. Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine. Int Clin Psychopharmacol 2001;16:145–51.
SHORT REPORT
Efficacy of milnacipran in the treatment of chronic pain syndromes MITSUHIRO KAMATA1, SHINGO NAITO2, HISASHI HIGUCHI3, AKIHITO SUZUKI4 & KOICHI OTANI4 Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Victoria on 12/16/14 For personal use only.
1Health Administration
Center, Yamagata University, Kojirakawa-machi, Yamagata, Japan, 2Department of Psychiatry, Akita City Hospital, Akita City, Akita, Japan, 3Department of Psychiatry, St. Marianna University School of Medicine, Kawasaki City, Kanagawa, Japan, and 4Department of Psychiatry,Yamagata University School of Medicine,Yamagata City,Yamagata, Japan
Abstract Eleven outpatients with chronic pain syndromes other than fibromyalgia were treated for 12 weeks with milnacipran, a novel serotonin noradrenaline reuptake inhibitor. The agent was administered at 50–150 mg/day, and the mean ⫾ SD dose at 12 weeks or at the time drug treatment was stopped was 84.1 ⫾ 32.2 mg/day. None of the patients met the DSM-IV criteria for a major depressive disorder. Abdominal, chest, back, arm, leg or glossal pain, or headache was involved. Pain was assessed clinically by means of a visual analog scale (VAS) before and 12 weeks after the start of milnacipran treatment, or at the time drug treatment was stopped. The mean ⫾ SD decrease in VAS scores was 42.3 ⫾ 31.6 (50.8 ⫾ 49.2%). One patient discontinued treatment after 4 weeks because of nausea, whereas others tolerated the agent well. These results suggest that the use of milnacipran in patients with a variety of chronic pain syndromes is beneficial. Key Words: Milnacipran, SNRI, antidepressant, chronic pain
Introduction Tricyclic antidepressants (TCAs) have long been considered the standard treatment for a variety of chronic pain syndromes [1–5]. Chronic pain is defined as pain that persists for longer than 3 months [1,6]. The effects of TCAs on both norepinephrine (NE) and serotonin (5-HT) are important because these neurotransmitters are thought to be involved in the pathogenesis of chronic pain syndromes [1,2,5]. Antidepressants have an effect on chronic pain syndromes independent of any effects on mood [1,7,8]. Despite the putative efficacy of TCAs in the treatment of chronic pain, their use has been compromised by the high degree of poorly tolerated adverse effects [1–5]. Newer antidepressants, which are non-TCAs with higher tolerance, have been studied for the treatment of chronic pain [2–4]. With regard to the analgesic effects to treat chronic pain, however, TCAs are more effective than noradrenaline reuptake inhibitor (NRIs), which are more effective than selective serotonin reuptake inhibitors (SSRIs) [9]. Therefore, it has been suggested that the ideal antidepressant agent for management of chronic pain would modulate both NE and 5-HT but lack the nontherapeutic synaptic effects associated with
TCAs or heterocyclic antidepressants [2]. A number of studies have documented the efficacy of serotonin norepinephrine reuptake inhibitors (SNRIs) in the treatment of chronic pain [1–3,5,10,11]. Milnacipran is a novel SNRI that is similar to imipramine, a TCA, with respect to both selectivity and absolute affinity [12]. However, this agent does not interact with post-synaptic receptors, giving it a favorable tolerance profile [13]. The efficacy of milnacipran in relieving pain has been documented in various types of chronic pain syndrome, including fibromyalgia [5]. We recently reported a case series describing the effects of milnacipran on various chronic pain syndromes, including abdominal pain, back pain, glossal pain, chest pain and headache [14]. Here, we present results from an open clinical trial, designed to quantify the efficacy of milnacipran to treat chronic pain syndromes other than fibromyalgia in more subjects than in our previous report [14]. Patients and methods Patients Eleven outpatients (two men, nine women) suffering from various types of chronic pain syndrome for at
Correspondence: Mitsuhiro Kamata. Tel: +81 23 628 4152. Fax: +81 23 628 4152. E-mail: [email protected] (Received 24 March 2009; accepted 24 August 2009) ISSN 1365-1501 print/ISSN 1471-1788 online © 2010 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS) DOI: 10.3109/13651500903282865
None None
Paroxetine 20 mg Fluvoxamine 75 mg None None None Paroxetine 20 mg Paroxetine 20 mg
None Paroxetine 30 mg
84.1 ⫾ 32.2
100 50
100 150 50 100 100 50 100
Etizolam 1 mg Alprazolam 1.2 mg, triazolam 0.25 mg, zolpidem 10 mg Brotizolam 0.25 mg Alprazolam 0.8 mg Zolpidem 10 mg Brotizolam 0.25 mg None None Etizolam 1 mg, alprazolam 1.2 mg, zolpidem 10 mg None None 75 50
least 3 months were initially enrolled in the study. Abdominal, chest, back, arm, leg or glossal pain, or headache was involved. Five of these patients were also included in our previous case series [14]. Participants had no evidence of serious or uncontrolled medical illness. Although one patient was being treated for angina pectoris and two patients were being treated for hypertension, their conditions remained stable during the study period. None of the patients met the DSM-IV criteria for a major depressive disorder, and none had depressive symptoms to a clinically significant degree. After presenting a complete description of the study to the patients, written informed consent was obtained. This study received ethics committee approval and was conducted in accordance with the ethical principles derived from the Declaration of Helsinki and the guidelines of the International Conference on Harmonization (ICH)/Good Clinical Practice (GCP). A summary of patient characteristics is outlined in Table I. Patient age was 66.7 ⫾ 17.4 years (mean ⫾ SD), and the duration of pain was 16.3 ⫾ 17.5 months (mean ⫾ SD).
16.3 ⫾ 17.5
Back pain Back pain
Abdominal and chest pain Back pain, headache Glossal pain Glossal pain, back pain Glossal pain Abdominal and back pain Arm, leg pain 4 33 12 15 5 3 60
4 3
Abdominal pain Abdominal pain, headache 16 24
Milnacipran treatment was started at 25 or 50 mg/day and was increased according to clinical response over 12 weeks. Patients suffering from insomnia were given drugs to treat the insomnia. All other medications were kept constant during the study. Only the dosage of milnacipran was changed, if necessary. Milnacipran was administered at 50–150 mg/day by the end of the 12-week period or by the time the drug treatment was stopped, and the dose of this agent at the end of the study was 84.1 ⫾ 32.2 (mean ⫾ SD) mg/day. Before the start of milnacipran treatment, four patients had been treated with paroxetine, and one had been treated with fluvoxamine, both SSRIs. To prevent acute withdrawal symptoms in these patients, a washout period was not used.
Mean ⫾ SD
66.7 ⫾ 17.4
F M 66 77 10 11
F M F F F F F 72 23 63 78 75 74 47 3 4 5 6 7 8 9
F F
Assessment
82 77
Type of pain Sex Age (years) Patient
69
Drug administration
1 2
Concomitant medications (mg/day) Milnacipran dose at end of study (mg/day) Duration of illness (months)
Table I. Patient characteristics and concomitant medications.
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Victoria on 12/16/14 For personal use only.
Previously used antidepressant (mg/day)
Efficacy of milnacipran on choronic pain syndromes
Chronic pain was assessed clinically by means of a visual analog scale (VAS) before and at 12 weeks after the start of milnacipran or at the time the drug treatment was stopped. Such assessments require patients to describe the intensity of their pain by placing a mark on a 100-mm line anchored by “no pain” at 0 mm and “worst imaginable pain” at 100 mm [15]. VAS scores before and at 12 weeks after the start of the milnacipran were compared. The Clinical Global Impressions-Severity of Illness scale (CGI-S) was used to assess the patients’ overall clinical condition [16]. The Clinical Global
70
M. Kamata et al.
Table II. Efficacy of milnacipran in the treatment of chronic pain syndromes. Patient
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Victoria on 12/16/14 For personal use only.
1 2 3 4 5 6 7 8 9 10 11 Mean ⫾ SD
% Change in VAS score
CGI-S score at Baseline
CGI-S score at end of study
CGI-I score at end of study
⫺87 ⫺79 ⫺42 ⫺86 ⫺14 ⫺80 ⫺80 60 ⫺11 ⫺89 ⫺ ⫺50.8 ⫾ 49.2
6 7 7 6 5 4 4 4 7 7 5 5.6 ⫾ 1.3
3 3 4 2 5 2 2 6 7 2 ⫺ 3.6 ⫾ 1.8
1 1 2 1 4 2 2 6 4 1 ⫺ 2.4 ⫾ 1.7
Impressions-Severity of Improvement scale (CGI-I) was also used [16].
Results The mean (⫾SD) VAS and CGI-S scores at baseline were 73.3⫾19.3 and 5.6⫾1.3, respectively. Ten patients continued milnacipran treatment and tolerated the drug well. One male patient withdrew from treatment without explanation, and one female patient stopped taking the drug at 4 weeks after the start of treatment because of nausea; thus, two patients stopped taking milnacipran. The mean (⫾SD) VAS score at endpoint was 30.7⫾27.2, which was a mean decrease (%) of 42.3⫾31.6 (50.8⫾49.2%). Table II shows the % decrease in VAS scores, changes in CGI-S score, and final CGI-I scores. The mean (⫾SD) CGI-S score was 3.6⫾1.8 at the end of the study. Four patients had a final CGI-I score of 1, “very much improved”, and three patients had a final CGI-I score of 2, “improved”. Two patients had a final CGI-I score of 4, “no change”. Chronic pain worsened in one patient after milnacipran treatment, and her VAS score changed from 50 to 80. Her final CGI-I score was 6, “much worse”.
drug. One patient experienced persistent nausea and thus discontinued treatment. Although nausea is the most common adverse effect of treatment with milnacipran [17], the rate of this adverse effect with milnacipran is relatively low compared to that with fluvoxamine [17]. Five patients had been treated with an SSRI before treatment with milnacipran. The daily dose of SSRIs used in these patients was the recommended therapeutic dose in Japan. There was little clinical improvement with SSRI treatment in these patients, but there was mild or marked clinical improvement with the milnacipran treatment. Pharmacological treatment with milnacipran was therefore beneficial for these patients. The present study found the use of milnacipran in patients with various chronic pain syndromes to be beneficial. Taken together with previous reports of the success of milnacipran in treating a wide range of chronic pain syndromes [5,10,14], this drug effectively relieves pain in chronic pain syndromes. Nevertheless, as this study was an open clinical trial without a placebo group, the reported improvements gained by patients who received milnacipran must be interpreted with caution. Furthermore, as the number of subjects was relatively small, the present results should be confirmed in a larger sample.
Discussion The patients in the present study showed a 50.8% decrease in VAS scores with milnacipran treatment, and seven patients showed some improvement in CGI-I score. Thus, these patients benefited from this treatment for chronic pain syndrome. Furthermore, six of the 11 patients were over 70 years of age and they tolerated the milnacipran well, despite their age. Accordingly, these results suggest that milnacipran is beneficial for the treatment of chronic pain in terms of both efficacy and tolerability. However, it should be noted that two patients stopped taking the
Key points • Chronic pain is defined as pain that persists for longer than 3 months • It has been suggested that the ideal antidepressant agent for management of chronic pain modulates both NE and 5-HT, but lacks the nontherapeutic synaptic effects associated with TCAs • Milnacipran, an SNRI, appears to be a useful agent in the treatment of a wide range of chronic pain syndromes
Efficacy of milnacipran on choronic pain syndromes Acknowledgement None. Statement of interest This study did not receive any financial or material support. The authors declare that they have no financial or other relationships relevant to the subject of this article.
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Victoria on 12/16/14 For personal use only.
References [1] Ansari A. The efficacy of newer antidepressants in the treatment of chronic pain: a review of current literature. Harvard Rev Psychiatry 2000;7:257–77. [2] Barkin RL, Fawcett J. The management challenges of chronic pain: The role of antidepressants. Am J Ther 2000;7:31–47. [3] Lynch ME. Antidepressants as analgesics: a review of randomized controlled trials. Pharmacol Pain 2001;26:30–36. [4] Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: An update and effect related to mechanism of drug action. Pain 1999;83:389–400. [5] Briley M. Clinical experience with dual action antidepressants in different chronic pain syndrome. Hum Psychopharmacol 2004;19:S21–5. [6] Bouckoms MB, Hackett TP. Pain patients. In: Cassem NH, editors. Massachusetts General Hospital Handbook of General Hospital Psychiatry. 4th ed. St. Louis, MO: Mosby-Yearbook, 1997:367–413. [7] Max MB. Treatment of post-herpetic neuralgia: antidepressants. Ann Neurol 1994;35(Suppl):S50–3. [8] Onghena P, Houdenhove BV. Antidepressant-induced analgesia in chronic non-malignant pain: A meta-analysis of 39 placebo-controlled studies. Pain 1992;49:205–19.
71
[9] Fishbain DA, Culter R, Rosomoff HL, Rossomoff RS. Evidence-based data from animal and human experimental studies on pain relief with antidepressants: A structured review. Pain Med 2000;1:310–6. [10] Leo RJ, Brooks VL. Clinical potential of milnacipran, a serotonin and norepinephrine inhibitor, in pain. Curr Opin Investig Drugs 2006;7:637–42. [11] Barkin RL, Barkin S. The role of venlafaxine and duloxetine in the treatment of depression with decremental changes in somatic symptoms of pain, chronic pain, and the pharmacokinetics and clinical considerations of duloxetine pharmacotherapy. Am J Ther 2005;12:431–8. [12] Moret C, Charveron M, Finberg JPM, Couzinier JP, Briley M. Biochemical profile of milnacipran (F 2207), 1-phenyl1-diethyl-aminocarbonyl-2-aminoethylcyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology 1985;24:1211–9. [13] Kasper S, Pletan Y, Solles A, Tournoux A. Comparative studies with milnacipran and tricyclic antidepressants in the treatment of patients with major depression: A summary of clinical trial results. Int Clin Psychopharmacol 1996; 11(Suppl 4):35–9. [14] Kamata M, Takahashi H, Naito S, Higuchi H. Effectiveness of milnacipran for the treatment of chronic pain: A case series. Clin Neuropharmacol 2004;27:208–10. [15] De Loach LJ, Higgins MS, Caplan AB, Stiff JL. The Visual Analog Scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesth Analg 1998;86:102–6. [16] Guy W. ECDEU assessment Manual for Psychopharmacology, Revised. US Dept Health, Education, and Welfare publication (ADM) 76–338. Rockville, MD: National Institute of Mental Health 1976. [17] Clerc G. Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine. Int Clin Psychopharmacol 2001;16:145–51.
