MORE HARD SCIENCE SUPPORTING THE TREATMENT OF DEPRESSIVE SYMPTOMS BY ADJUSTING THE THYROID FUNCTION.

CNS Drugs. 2010 Feb 1;24(2):131-61. doi: 10.2165/11530280-000000000-00000.

Therapeutic options for treatment-resistant depression.

Shelton RC, Osuntokun O, Heinloth AN, Corya SA.

Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Treatment-resistant depression (TRD) presents major challenges for both patients and clinicians. There is no universally accepted definition of TRD, but results from the US National Institute of Mental Health’s (NIMH) STAR*D (Sequenced Treatment Alternatives to Relieve Depression) programme indicate that after the failure of two treatment trials, the chances of remission decrease significantly. Several pharmacological and nonpharmacological treatments for TRD may be considered when optimized (adequate dose and duration) therapy has not produced a successful outcome and a patient is classified as resistant to treatment. Nonpharmacological strategies include psychotherapy (often in conjunction with pharmacotherapy), electroconvulsive therapy and vagus nerve stimulation. The US FDA recently approved vagus nerve stimulation as adjunctive therapy (after four prior treatment failures); however, its benefits are seen only after prolonged (up to 1 year) use. Other nonpharmacological options, such as repetitive transcranial stimulation, deep brain stimulation or psychosurgery, remain experimental and are not widely available. Pharmacological treatments of TRD can be grouped in two main categories: ‘switching’ or ‘combining’. In the first, treatment is switched within and between classes of compounds. The benefits of switching include avoidance of polypharmacy, a narrower range of treatment-emergent adverse events and lower costs. An inherent disadvantage of any switching strategy is that partial treatment responses resulting from the initial treatment might be lost by its discontinuation in favour of another medication trial. Monotherapy switches have also been shown to have limited effectiveness in achieving remission. The advantage of combination strategies is the potential to build upon achieved improvements; they are generally recommended if partial response was achieved with the current treatment trial. Various non-antidepressant augmenting agents, such as lithium and thyroid hormones, are well studied, although not commonly used. There is also evidence of efficacy and increasing use of atypical antipsychotics in combination with antidepressants, for example, olanzapine in combination with fluoxetine (OFC) or augmentation with aripiprazole. The disadvantages of a combination strategy include multiple medications, a broader range of treatment-emergent adverse events and higher costs. Several experimental pharmaceutical treatment alternatives for TRD are also being explored in combination with antidepressants or as monotherapy. These less studied alternative compounds include pindolol, inositol, CNS stimulants, hormones, herbal supplements, omega-3 fatty acids, S-adenosyl-L-methionine, folic acid, lamotrigine, modafinil, riluzole and topiramate. In summary, despite an increasing variety of choices for the treatment of TRD, this condition remains universally undefined and represents an area of unmet medical need. There are few known approved pharmacological agents for TRD (aripiprazole and OFC) and overall outcomes remain poor. This might be an indication that depression itself is a heterogeneous condition with a great diversity of pathologies, highlighting the need for careful evaluation of individuals with depressive symptoms who are unresponsive to treatment. Clearly, more research is needed to provide clinicians with better guidance in making those treatment decisions–especially in light of accumulating evidence that the longer patients are unsuccessfully treated, the worse their long-term prognosis tends to be.

Nord J Psychiatry. 2010 Jan 21. [Epub ahead of print]

Thyroid autoimmunity and treatment response to escitalopram in major depression.

Eller T, MetskÃ¼la K, Talja I, Maron E, Uibo R, Vasar V.

Department of Psychiatry, University of Tartu, Raja 31, 50417 Tartu, Estonia.

Background: There is evidence that immune alterations play an important part in the pathogenesis of major depression. Thyroid autoimmunity has been found in association with major depression in several studies. Aim: 1) to examine whether the prevalence of anti-thyroid peroxidase autoantibodies (anti-TPO) in depressive patients differs from that in healthy controls; 2) to investigate the possible relationship between thyroid autoimmunity, total T3, free T3, free T4, thyroid-stimulating hormone (TSH), clinical status and treatment outcome in depression. Method: The study group consisted of 129 outpatients (69.8% female; mean age 31.7+/-12.0 years) with major depressive disorder with a Montgomery-Azsberg Depression Rating Scale total score of 22 or higher and 72 healthy controls (62.5% female; mean age 31.7+/-13.1 years). The patients were treated with escitalopram 10-20 mg/day for 12 weeks using open-label placebo non-controlled design. Anti-TPO, total T3, free T3, free T4 and TSH were measured before the treatment. Results: The anti-TPO was found in eight (8.9%) depressive and two (4.8%) healthy females without statistical difference between these groups. Since anti-TPO was not seen in males, all further statistical analyses were carried out in females. At the end of week 12 of the treatment, 60 female patients (66.7%) were defined as responders and 30 depressive females (33.3%) showed insufficient response to treatment. Although there were no significant differences in the measurements between responders and non-responders, the last group showed a trend for a higher prevalence of anti-TPO compared with responders. Conclusion: Thyroid autoimmunity might be a factor predicting treatment response to antidepressants in depressive patients.

PMID: 20088751 [PubMed – as supplied by publisher]

Psychiatry Res. 2010 Jan 30;175(1-2):74-7. Epub 2009 Dec 9.

Changes in hypothalamic-pituitary-thyroid axis following successful treatment with low-frequency right prefrontal transcranial magnetic stimulation in treatment-resistant depression.

Kito S, Hasegawa T, Fujita K, Koga Y.

Department of Neuropsychiatry, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. kito@kk.iij4u.or.jp

Hypothalamic-pituitary-thyroid (HPT) axis abnormalities have been reported in some patients with major depression. To knowledge, however, the effects of low-frequency right prefrontal transcranial magnetic stimulation (TMS) on the HPT axis have not yet been elucidated. The goal of this study was to evaluate alterations in the HPT axis associated with the therapeutic efficacy of TMS treatments. Twenty patients with treatment-resistant depression received five 60-s 1-Hz trains over the right dorsolateral prefrontal cortex. Twelve treatment sessions were administered within a 3-week period (total pulses, 3600). Responders were defined as a > or =50% decrease in the Hamilton Depression Rating Scale (HDRS) score. Serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) were measured, respectively, at pre- and post-treatment. There were no significant changes in fT3 and fT4 levels measured at either pre- or post-treatment in either responders or nonresponders; however, TSH levels of responders elevated significantly after TMS treatments. In addition, there was a significant negative correlation between TSH levels at pretreatment and decrease (%) in the HDRS score. These findings suggest that the HPT axis is associated with antidepressant effects of low-frequency right prefrontal TMS, and indicate that lower TSH levels at pre-treatment are correlated with better therapeutic efficacy.

PMID: 20004482 [PubMed – indexed for MEDLINE]

Psychoneuroendocrinology. 2009 Nov 23. [Epub ahead of print]

Thyroid function 48h after delivery as a marker for subsequent postpartum depression.

Albacar G, Sans T, MartÃn-Santos R, GarcÃa-Esteve L, Guillamat R, Sanjuan J, CaÃ±ellas F, Carot JM, GratacÃ²s M, Bosch J, Gaviria A, Labad A, Zotes AG, Vilella E.

University Psychiatric Hospital Institut Pere Mata, IISPV, University Rovira i Virgili, Reus, Spain.

Physiological changes during gestation and after delivery are associated with postpartum thyroid dysfunction, which is due to thyroid autoimmunity in some cases. Postpartum thyroid dysfunction, in turn, has been associated with postpartum depression (PPD). The aim of the present study was to evaluate whether thyroid function immediately after delivery can predict postpartum depression at 8 weeks and 32 weeks after delivery. This study examined 1053 postpartum Spanish women without a previous history of depression. We evaluated depressive symptoms at 48h, 8 weeks and 32 weeks postpartum and used a diagnostic interview to confirm major depression for all probable cases. Free thyroxin (fT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb) and C-reactive protein (CRP) were assayed at 48h postpartum. Binary and multivariate logistic regression analyses were performed to determine independent risk factors for PPD. Although 152 women (14.4%) had high TPOAb (>27IU/mL) and slightly elevated TSH concentrations with normal fT4, we did not find any association between thyroid function and PPD. This thyroid dysfunction was not associated with CRP concentrations that were outside of the normal range (>3mg/L). We conclude that thyroid function at 48h after delivery does not predict PPD susceptibility.

PMID: 19939574 [PubMed – as supplied by publisher]

World J Biol Psychiatry. 2009;10(4):324-9.

Depressive disorder and thyroid axis functioning during pregnancy.

Bunevicius R, Kusminskas L, Mickuviene N, Bunevicius A, Pedersen CA, Pop VJ.

Institute of Psychophysiology and Rehabilitation, Kaunas University of Medicine, LT-00135 Palanga, Lithuania. rob@ktl.mii.lt

BACKGROUND: Depression and thyroid dysfunction are prevalent in women, including pregnant women. The aim of this study was to assess the relationship between depression and thyroid function during pregnancy. METHODS: One hundred and ninety-nine pregnant women three times during pregnancy were assessed for depressive disorder and for thyroid stimulating hormone (TSH) and free thyroxine (FT(4)) concentrations. RESULTS: Prevalence of depressive disorder was 6.5% in early pregnancy, 3.0% in middle pregnancy and 3.5% in late pregnancy. There were no women with overt thyroid dysfunction. Subclinical hyperthyroidism was found in 23% of women in early pregnancy, in 5% of women in middle pregnancy and in 6% of women in late of pregnancy. In late pregnancy depressed women compared to non-depressed women had significantly higher FT(4) concentrations and a strong trend towards lower TSH concentrations as well as higher prevalence of subclinical hyperthyroidism. CONCLUSIONS: These findings show an association between thyroid dysfunction and depression in late pregnancy. Because gestational depression might interfere with pregnancy outcome, evaluation of thyroid function during gestation is warranted.

PMID: 19921974 [PubMed – indexed for MEDLINE]

Eur J Endocrinol. 2009 Dec;161(6):917-21. Epub 2009 Sep 15.

Treated hypothyroidism, cognitive function, and depressed mood in old age: the Rancho Bernardo Study.

Kramer CK, von MÃ¼hlen D, Kritz-Silverstein D, Barrett-Connor E.

Division of Epidemiology, Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093-0607, USA.

OBJECTIVE: Overt hypothyroidism is associated with cognitive impairment, which can be reversed if treated early and appropriately. We compared cognitive function (CF) of euthyroid older adults with those who had long-term treated hypothyroidism. METHODS: Between 1999 and 2003, the CF of 885 euthyroid and 149 hypothyroid-treated older adults (primary hypothyroidism after surgery or autoimmune thyroid disease) was assessed using three standardized CF tests: the modified mini-mental state examination, Trails B, and verbal fluency. Depressed mood was assessed using the Beck Depression Inventory (BDI). Only participants with thyroid stimulating hormone (TSH) in the normal range were included. RESULTS: The treated hypothyroid group had been treated with l-thyroxine for an average of 20 years. Those with treated hypothyroidism were older than the euthyroid group (76.1+/-9.6 vs 73.6+/-10.2 years, P=0.005) and were much more often women (81.6 vs 54.8%, P<0.001). TSH levels were similar between groups (median interquartile range=1.57 (1.19) vs 1.54 (1.59) mIU/l, P=0.81). Compared to euthyroid, the treated hypothyroidism group had more frequent antidepressant medication use (19.5 vs 8.5%, P<0.001) but similar BDI scores. Performance on the three CF tests did not differ by thyroid hormone treatment. Results were not changed after adjustment for age, sex, antidepressant medication use, exercise, and total cholesterol. CONCLUSION: Long-term treated hypothyroidism is not associated with impaired CF or depressed mood in old age. The lack of association with CF is reassuring with regard to long-term use of thyroid hormone therapy.

Bradford S. Weeks, M.D

The Weeks Clinic for Corrective Medicine and Psychiatry

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Science supporting treatment of depressive Sx with thyroid meds.