Innovations In Clinical Neuroscience

MAR-APR 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 4 , N U M B E R 3 – 4 , M A R C H – A P R I L 2 0 1 7 ] 27 titrated up to 30mcg/day in a subject who had received phenelzine for at least four weeks prior. 38 The two latter cases described the efficacy of enhancement of the MAO-I effect with T3. These two subjects had trials of TCA monotherapy and TCA in combination with lithium or TCA in combination with T3 prior to receiving phenelzine in combination with T3. 39 TREATMENT AND MONITORING Laboratory studies and frequency of monitoring are detailed in Table 3. We recommend deferring the administration of T3 to a patient with abnormally high or low thyroid-stimulating hormone (TSH) level for further evaluation. However, low or high free T3 or free T4 levels in the context of a normal TSH does not preclude treatment with T3, as these elevations or decreases may be physiological or due to concurrent medications. Prior to prescribing T3, the patient and clinician should discuss and document the risk-benefit profile of T3, including risk for arrhythmia and osteoporosis. Throughout treatment the risks and benefits of T3 should be re- evaluated, focusing on depressive symptoms or cardiovascular status. If efficacy has been demonstrated and there are no symptoms of hyperthyroidism and no known cardiac disease, consider maintenance T3 supplementation even if the TSH level is below the normal reference range. 40 Doses above 50mcg daily and long- term therapy with T3 may be reasonable if the patient has a history of multiple depressive episodes or significant treatment resistance, despite limited data. 40 In an observational study of 14 patients, no subjects developed any cardiac or skeletal disease after receiving doses from 25- to 150mcg over a two- year period. 41 In pre- and postmenopausal women receiving T4 (levothyroxine), there was no clinically significant difference in bone mineral density between groups after one year, but bone density did decrease in post- menopausal women compared to the population standard. 42 CONCLUSION Most trials that evaluated T3 enhancement or augmentation were published earlier than 10 years ago using small samples of patients, and there are limited data available for liothyronine's efficacy with newer antidepressants. The majority of reports TABLE 2. SSRI and T3 trials STUDY AUTHORS DESIGN (N) TREATMENT RESULTS Abraham et al, 33 2006 Open-label (12); Augmentation SSRI (sertraline, citalopram, fluvoxamine, or paroxetine) + T3 25mcg/day x 1 week, then 50 mcg/day if tolerated 5 subjects (42%) achieved response a ; 3 subjects (25%) reached remission b Agid and Lerer, 34 2003 Open-label (25) Augmentation SSRI (fluoxetine or paroxetine 40mg/day) + T3 25–50mcg/day 10 subjects (40%) achieved response c ; 9 subjects (36%) reached remission b Appelhof et al, 31 2004 Randomized, double- blind (106); Enhancement Paroxetine 30mg/day + T3 25mcg/day or T3 25mcg BID or placebo No significant difference in response rates Cooper-Kazaz et al, 30 2007 Randomized double-blind (124); Enhancement Sertraline 50mg/day x 1 week, then 100mg/day + T3 20–25mcg/day x 1 week, then 40–50mcg/day or placebo T3 vs. placebo: 70% response rate vs. 50% (p = 0.02); 58% remission rate vs. 38% (p = 0.02) Garlow et al, 32 2012 Randomized double-blind (153); Enhancement Sertraline flexibly dosed d , + T3 25mcg/day x 1 week, then 50mcg/day or placebo No significant difference in response and remission rates Iosifescu et al, 35 2005 Open-label (20); Augmentation SSRI (fluoxetine, sertraline, paroxetine, citalopram or escitalopram) + T3 50mcg/day as augmentation HRSD decreased from 20.5±3.6 to 14±7.1 (p <0.001); 7 subjects were responders (35%); 6 subjects reached remission (30%) BID: twice daily; HRSD: Hamilton Rating Scale for Depression; T3: liothyronine/triiodothyronine a : ≥50% decrease in HRSD b : HRSD ≤7 c : Clinical Global Improvement-B subscale (CGI-B) >3 d : 50mg/day x 1 week, then increased in 50mg increments weekly based on response/tolerability to maximum of 200mg/day

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