Article

Rapid antidepressant response after nocturnal TRH administration in patients with bipolar type I and bipolar type II major depression.

Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, University Science Center, 3535 Market Street, Philadelphia, PA 19104, USA.
Journal of Clinical Psychopharmacology (Impact Factor: 3.76). 09/2005; 25(4):325-30. DOI: 10.1097/01.jcp.0000169037.17884.79
Source: PubMed

ABSTRACT Thyrotropin-releasing hormone (TRH) is a tripeptide that produces endocrine and behavioral effects in animals and humans. Some studies have shown transient antidepressant activity after morning administration of TRH. We hypothesized that nocturnal administration of TRH, when the circadian sensitivity of the TRH receptor is at its peak, may result in a more robust antidepressant effect.
Twenty patients with bipolar (BP) type I or BP type II major depressive episode (MDE) were given nocturnal intravenous TRH 500 microg (n = 10) or saline (n = 10) at midnight in a randomized, double-blind fashion. Antidepressant activity was assessed using the Hamilton Depression Rating (HAM-D), Young Mania Rating (YMR), and Profile of Mood (POMS) scales over a 48-hour period. Thyrotropin (TSH), total T4, and free T3 concentrations were measured before and after TRH administration. Data were analyzed using chi test, Fisher exact test, and repeated-measures ANOVA.
Sixty percent of the TRH group and 10% of the saline group showed a > or =50% reduction in baseline total HAM-D score within 24 hours (P = 0.03). HAM-D ratings fell by an average of 52% after TRH administration versus 12% after saline administration (P = 0.038). There was a modest increase in YMR scores after TRH compared with saline (P < 0.032). No manic or hypomanic episodes were observed. Antidepressant effects of TRH lasted up to 48 hours. There was no correlation between DeltaTSH, DeltaT4, or DeltaT3 measures after TRH (or saline) administration and the change in HAM-D scores.
Nocturnal TRH administration may produce a rapid antidepressant effect in some patients with BP I and BP II MDE.

0 Followers
 · 
45 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although No-Type I Bipolar spectrum disorders (NBP-I) are common, recurrent, and disabling, they are underdiagnosed and misdiagnosed in clinical practice. Several data show that NBP-I (especially BP type II) are a significant public health problem, and there is a dearth of studies of effective treatment modalities for the control of acute symptoms and the prevention of mood recurrences (mainly major depressive episodes). Considering the growing need to find effective therapies for patients with NBP-I, this review is based on a systematic search of evidence about the efficacy of treatments for each phase of the NBP-I. Fifty-seven studies were identified and reviewed. Most studies investigating the pharmacotherapy of NBP-I were methodologically limited, having observational or retrospective designs and small samples. Regarding short-term treatment, there is some limited support for the use of risperidone, valproate, and quetiapine in hypomania, and for valproate, quetiapine, fluoxetine, and venlafaxine in treating depression. For long-term treatment, the only preventive therapy for both depression and hypomania that is supported by several controlled studies is quetiapine. Lithium and fluoxetine have shown efficacy in delaying depressive recurrences. Although the adequate treatment for these patients remains to be determined, mood stabilizers and some forms of psychotherapy may be useful for these patients. We conclude that there is a paucity of sound evidence to guide clinicians in treating NBP-I patients. Although progress has been made, more quality research is needed to delineate effective treatment strategies.
    Current Psychiatry Reviews 02/2013; 9(1):41-50. DOI:10.2174/1573400511309010006
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have provided evidence of subtle thyroid hormone metabolism abnormalities in patients with mood disorders. Although these studies are informative, the precise role of the hypothalamic-pituitary-thyroid axis in bipolar disorder, especially in women, remains unclear. We sought to further corroborate thyroid function in patients with bipolar disorder in comparison to patients with other psychiatric, as well as non-psychiatric, diagnoses. In this retrospective, cross-sectional, naturalistic study, serum thyroid-stimulating hormone (TSH) levels in a total sample of 3,204 patients were compared. The study sample included patients with bipolar disorder (n = 469), unipolar depression (n = 615), and other psychiatric diagnoses (n = 999), patients from endocrinology clinics (n = 645), and patients from dermatology clinics (n = 476). Analyses were completed using two different normal ranges for TDH: a high normal range (0.4-5.0 μIU/mL) and a low normal range (0.3-3.0 μIU/mL). Patients with bipolar disorder showed significantly higher serum TSH levels compared to all other groups. In women, the rate of above normal range TSH was highest in patients with bipolar disorder for both high (5.0 μIU/mL; 12.1%) and low (3.0 μIU/mL; 30.4%) upper normal limits. In patients with bipolar disorder, serum TSH levels did not differ significantly between different mood states. In the lithium-treated patients (n = 240), a significantly lower percentage of women (55.9%) compared to men (71.2%) fell within the 0.3-3.0 μIU/mL normal TSH window (p = 0.016). For the high normal range (0.4-5.0 μIU/mL), serum lithium levels above 0.8 mmol/L were associated with a significantly lower proportion of female patients (59.2%) falling within the normal range than male patients (88.9%). Non-lithium treatment was not associated with a gender difference. Our findings show a higher rate of TSH abnormality in patients with bipolar disorder, particularly those taking lithium, compared to those with other psychiatric and medical conditions. Lithium-associated thyroid dysregulation occurs more frequently in female patients. Using the low normal range TSH values at follow-up can increase sensitivity in recognizing hyperthyroidism in lithium-treated female patients, and help in preventing the development of subclinical hypothyroidism and an adverse course of illness.
    Bipolar Disorders 12/2013; DOI:10.1111/bdi.12163 · 4.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: GH-releasing hormone (GHRH) is a key regulator of GH secretion. The role of GH in anxiety is somewhat contradictory. The aim of this study is to elucidate the consequences of lack of GHRH on emotional behaviour in a mouse model of GH deficiency due to removal of the GHRH gene (GHRH knock out, GHRHKO). Design: Homozygous GHRHKO and wild type male mice were utilized for this study. The emotional behaviour was measured through a battery of behavioural tests (locomotor activity/open field, light-dark exploration, elevated plus maze, forced swim test, tail suspension test). To correlate the emotional behaviour with brain neurochemistry, we evaluated thyrotropin-releasing hormone (TRH) gene expression in hypothalamic tissue by real-time PCR, and the levels of norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) in prefrontal cortex by HPLC analysis. Results: GHRHKO mice showed increased exploratory activity. In the open field test (P < 0.005), light-dark box (P < 0.005) and elevated plus maze (P < 0.05), GHRHKO mice demonstrated a decrease in anxiety-related behaviour. In addition, GHRHKO mice showed reduced immobility time with respect to control in forced swim test and tail suspension test (P < 0.0001). The gene expression of hypothalamic TRH (P < 0.05) was increased, while NE levels in prefrontal cortex were decreased compared to control (P < 0.05). Conclusion: These results suggest that in male mice GHRH deficiency brings about an increased physical activity and decreased anxiety- and depression-related behaviour, possibly related to increased TRH and decreased NE levels in the brain.
    Growth Hormone & IGF Research 06/2014; 24(5). DOI:10.1016/j.ghir.2014.06.004 · 1.33 Impact Factor