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Psychosomatic Medicine 62:461-462 (2000)
© 2000 American Psychosomatic Society

LETTERS TO THE EDITOR

Sertraline in Diabetic Neuropathy: Response and Biology

Paul J. Goodnick, MD, Liana Mendosa, MD, Adarsh Kumar, PhD, Blanche Freund, PhD and C. Lindsay DeVane, PhD

Department of Psychiatry & Behavioral Sciences, University of Miami School of Medicine, Miami, Florida and Department of Pharmacology, Medical University of South Carolina

Serotonin has been shown to have an important role in glucose use (1). Pain pathways, in contrast to gluconeogenesis, include both norepinephrine and serotonin neurons. Thus, it is not surprising that tricyclic antidepressants, focusing on norepinephrine, have treated diabetic neuropathy successfully. However, these medications are limited in usefulness in diabetes mellitus, because they can worsen diabetic control (1). Therefore, attention has turned to serotonin-based treatments, eg, the selective serotonin reuptake inhibitors (SSRI). In previous work, it was found that sertraline (SRT) at 50 mg/day was able to successfully treat comorbid major depression and diabetes mellitus, while reducing HbA1c levels (2). Furthermore, in an initial study, it was reported that at doses increased to 150 mg/day, SRT was successful in ameliorating symptoms of diabetic neuropathy (3). This study was developed to attempt a replication of the previous results using a lower minimal dose of sertraline while also integrating levels of HbA1c levels with those of pain, platelet 5-HT content, and plasma sertraline levels.

After obtaining informed consent, patients needed to meet inclusion criteria for diabetic neuropathy. Patients were excluded if they met criteria for major depressive disorder or other major psychiatric disorder. Patients were given an average dose of 62 mg of SRT per day for an 8-week period. They were evaluated at their baseline level and after 1, 2, 4, and 8 weeks for the following: 1) visual analog scale (0–100 mm) on each of pain, paresthesia, numbness; 2) MD observer rating (0–2) on each of pain, paresthesia, numbness; 3) Hamilton Depression Rating Scale (HDRS); and 4) Beck Depression Inventory (BDI). Furthermore, blood samples were collected at baseline and final ratings for platelet (Plt) serotonin content and HbA1c, as well as a final blood sample for evaluation of plasma sertraline level.

Twelve subjects (7 men, 5 women) participated with a mean age of 57.8 + 4.2 years and a mean duration of diabetic neuropathy of 3.9 years. Mean baseline Hamilton Depression Rating Scale (HDRS) was 3.2 + 2.7; mean final HDRS was 0.4 + 0.5. Mean baseline Beck Depression Index (BDI) was 8.5 + 8.5; mean final BDI was 5.1 + 6.4. In terms of clinical response, pain, paresthesias, and numbness, all improved significantly on both self- and physician-ratings (all improvements at p <= .01 at week 1 and thereafter) (Table 1). In seven patients with complete data, HbA1c levels improved from 9.4 + 1.9 to 8.8 + 1.5 (t = 2.1, p < .08). Platelet 5-HT content fell from 49.9 + 6.2 to 6.2 + 5.5 ng/108 Plt (t = 8.1, p << .01). Mean plasma sertraline level was 11.3 + 7.3 ng/ml. Mean baseline ratings of platelet 5-HT content correlated significantly to later improvements in MD measurement of pain (r = .65, p = .05). Plasma sertraline levels correlated significantly with improvement in self-rating of numbness (r = .69, p < .05) and showed a trend for MD ratings of numbness (r = .62, p <.08).


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  		Table 1. Neuropathy Symptoms Response to Sertraline
 
In previous work, it was shown that a maximum dose of 150 mg of sertraline per day was effective for treatment of diabetic neuropathy (3). In this study, in an open trial at a mean dose of 62 mg/day, it was shown that sertraline was effective in ameliorating the pain, paresthesias, and numbness associated with diabetic neuropathy in both self-ratings and observer ratings. Also, previous data suggesting that SRT can reduce HbA1c levels (2) was partly replicated in showing a trend in a small subsample of seven patients. Clearly, both results need additional replication in larger samples in double-blind studies. In addition, evidence that SRT has the effect to reduce platelet 5-HT content was replicated from previous studies (2, 3). This can be related to serotonin reuptake blockade, preventing reentry of serotonin into platelets. Furthermore, previous results showing an association of baseline 5-HT content to clinical improvement in neuropathy (3) were replicated, here finding an association with MD ratings of pain relief. This builds on other data that have shown an association of baseline platelet 5-HT content to SSRI-related improvement in depression (2, 4). More controlled double-blind studies are indicated of this possible inexpensive predictor of improvement to SSRI. Finally, plasma sertraline levels were found related possibly to SRT benefits for numbness; this partly replicates previous reports of the relation of SRT relevance to improvement in clinical findings in neuropathy (3). Once again, further double-blind investigation is warranted.

REFERENCES

  1. Lustman PJ, Griffith LS, Clouse RE, Freedland KE, Eisen SA, Rubin EH, Carney RM, McGill JB. Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial. Psychosom Med 1997; 59: 241–50.[Abstract/Free Full Text]
  2. Goodnick PJ, Kumar A, Henry JH, Buki VM, Goldberg RB. Sertraline in coexisting major depression and diabetes mellitus. Psychopharmacol Bull 1997; 33: 261–4.[Medline]
  3. Goodnick PJ, Jimenz I, Kumar A. Sertraline in diabetic neuropathy: preliminary results. Ann Clin Psychiatry 1997; 9: 255–7.[Medline]
  4. Goodnick PJ, Henry J, Kumar A. Neurochemistry and paroxetine response in major depression. Biol Psychiatry 1995; 37: 417–9.[Medline]




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