leuprolide and Depressive-Disorder

The author's aim is to aid primary care physicians and obstetrician-gynecologists in correctly diagnosing and treating premenstrual dysphoric disorder (PMDD). The symptoms fluctuate markedly, but their timing is key. PMDD patients experience symptoms only during the luteal phase and will have a symptom-free interval after the menstrual flow and before ovulation. The author discusses self-report instruments, which are valuable tools for diagnosis when combined with the ICD-10 criteria for premenstrual syndrome (PMS) or the DSM-IV criteria for PMDD and the ruling out of medical and psychiatric conditions, such as diabetes, hypothyroidism, major depression, and dysthymia, that cause similar symptoms. Treatment strategies ranging from nonpharmacologic approaches such as dietary modification and aerobic exercise to pharmacologic interventions such as antidepressants, anxiolytics, and agents to suppress ovulation are examined.

Topics: Anti-Anxiety Agents; Antidepressive Agents; Buserelin; Danazol; Depressive Disorder; Diagnosis, Differential; Estrogen Antagonists; Female; Gynecology; Humans; Leuprolide; Medical Records; Obstetrics; Ovulation; Practice Patterns, Physicians'; Premenstrual Syndrome; Primary Health Care; Professional Practice; Psychiatric Status Rating Scales; Severity of Illness Index

The gonadotropin-releasing hormone (GnRH) agonists are a relatively new class of drugs that are potentially effective in treating disorders that are aggravated either by estrogen or testosterone. GnRH agonists are effective in the treatment of endometriosis, as well as other disorders, such as advanced prostrate cancer, precocious puberty and uterine leiomyomata. While the GnRH agonists reduce the extent of the endometrial lesions and the occurrence of pelvic pain associated with endometriosis, these agents are associated with physical and psychiatric side effects. The adverse effects of these agents are consistent with the physiological effects of ovarian suppression, such as vasomotor instability, vaginal dryness, and headaches. Preliminary results of a prospective, double-blind placebo-controlled study and an open label trial indicates that depressive mood symptoms increase in women treated with GnRH agonist therapy for endometriosis. Additional evidence suggest that sertraline effectively manages depressive mood symptoms associated with GnRH agonist therapy. The reason for the decline in mood on GnRH agonists is postulated to be associated with the decline in estrogen levels. Effective treatment strategies for depressive mood symptoms in women on GnRH agonists therapy may offer insight into the mechanisms of action of estrogen on mood.

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder; Double-Blind Method; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Nafarelin; Randomized Controlled Trials as Topic; Sertraline

The results of several recent studies suggest that estrogen and testosterone play an important role in the modulation of mood and cognitive function in women, and preliminary evidence indicates that these hormones may also modulate the levels of beta-amyloid (Abeta), a 4 Kilo Dalton peptide that is likely to be involved in the pathogenesis of Alzheimer's disease. However, the physiological and clinical effects of reversible castration remain unclear and no systematic data is currently available for men. We designed the present study to investigate the effects of reversible chemical castration on the mood and cognitive performance of men treated for prostate cancer, as well as its impact on the levels of plasma Abeta. Forty men with prostate cancer were clinically treated with androgen blockade therapy (flutamide and leuprolide) for 36 weeks and subsequently followed up for another 18 weeks after treatment was discontinued. All subjects received a comprehensive clinical, neuropsychological and biochemical evaluation that included the use of the Beck Depression (BDI) and Anxiety Inventories (BAI), several subtests of the Wechsler Memory and Intelligence Scales (Word Lists-WL, Verbal Paired Associates-VPA, Visual Reproduction-VR and Block Design-BD), and biochemical monitoring of changes in estrogen, testosterone and Abeta levels. Chemical castration was associated with a rapid and marked decline in the levels of testosterone and estradiol, and significant increase in plasma Abeta levels. Treatment was associated with increased BDI (p = 0.004) and BAI scores (p < 0.001), although such changes were of questionable clinical significance (i.e., few subjects had scores > or = 13). CAMCOG (p = 0.046) and WL recall total scores (p < 0.001) improved significantly after androgen blockade treatment was discontinued, but visuospatial abilities, as assessed by BD, was not influenced by the introduction or discontinuation of treatment. There was a significant negative correlation between changes in Abeta levels and subjects' WL total score change between weeks 36 and 54 (r = -0.452, p = 0.012). The results of this naturalistic study indicate that chemical castration is associated with a significant rise in the plasma levels of Abeta and, clinically, with increased depression and anxiety scores. The discontinuation of treatment is associated with better cognitive performance, most noticeably of verbal memory. The performance of subjects on the WL test was negatively corr

Topics: Adult; Affect; Aged; Aged, 80 and over; Amyloid beta-Peptides; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Anxiety Disorders; Cognition; Depressive Disorder; Estradiol; Flutamide; Follow-Up Studies; Humans; Hypogonadism; Leuprolide; Male; Memory; Middle Aged; Multivariate Analysis; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Gonadotropin-releasing hormone agonist (GnRHa) in depot form for once-a-month rather than daily injection was examined in a small open trial to determine the extent of reduction of premenstrual symptoms, particularly premenstrual "depression.". Women who met criteria for premenstrual syndrome (PMS) or for PMS with comorbidity of major depression (MD), based on DSM-III-R criteria, were evaluated for the study. Evaluation included Structured Clinical Interview for DSM-III-R, administered in the follicular phase, and Daily Symptom Report (DSR), maintained throughout the study. Seven PMS subjects and two subjects who met the severity and change criteria for PMS but had concurrent MD were administered 3.75 mg of depot leuprolide monthly. Symptom change as reported on the DSR was compared with the untreated baseline scores.. Six of seven PMS subjects had cessation of menses and significant decreases in premenstrual symptoms (p < .0001), which were reduced to their follicular phase levels. Physical symptoms of swelling and breast tenderness were among the most improved symptoms. Despite cessation of menses, the two MD subjects showed little improvement in premenstrual symptoms and no improvement in depressive symptoms. The premenstrual depression scores decreased almost completely in the PMS subjects, but increased slightly in the MD subjects.. This small open trial suggests that GnRH agonist therapy reduces premenstrual symptoms including "depression" in women who meet criteria for PMS but not in women with PMS and MD. Further controlled study of the role of ovarian function in mood disorders is needed.

Topics: Adult; Comorbidity; Delayed-Action Preparations; Depressive Disorder; Female; Humans; Leuprolide; Pilot Projects; Premenstrual Syndrome; Psychiatric Status Rating Scales

There is no consensus on the association between the use of androgen deprivation therapy (ADT) and the risk of developing depression. This study investigated the association between ADT use and the development of depression, outpatient psychiatric services, inpatient psychiatric services, and suicide in a homogeneous group of men with prostate cancer (PC) treated with definitive radiation therapy (RT) after controlling for multiple sources of selection bias.. This was a retrospective, observational cohort study of 39,965 veterans with PC who were treated with definitive RT and were diagnosed by the US Department of Veterans Affairs health care system between January 1, 2001, and October 31, 2015. Exposure was ADT initiation within 1 year of the PC diagnosis. The primary outcome was new development of depression. Secondary outcomes were outpatient psychiatric use, inpatient psychiatric use, and suicide.. During follow-up, 934 patients were newly diagnosed with depression, 7825 patients used outpatient psychiatric services, 358 patients used inpatient psychiatric services, and 54 patients committed suicide. In the multivariable competing risks regression model, ADT was associated with the development of depression (subdistribution hazard ratio [SHR], 1.50; 95% confidence interval [CI], 1.32-1.71; P < .001). ADT was also associated with outpatient psychiatric utilization (SHR, 1.21; 95% CI, 1.16-1.27; P < .001). Finally, ADT was not associated with inpatient psychiatric utilization or suicide.. An increase in the risk of depression and the use of outpatient psychiatric services was observed in a large cohort of men with PC who received ADT with definitive RT. These results may provide further evidence for the long-term risks of ADT for psychiatric health in the treatment of PC.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Depression; Depressive Disorder; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Hospitalization; Humans; Imidazolidines; Leuprolide; Male; Mental Health Services; Middle Aged; Nitriles; Oligopeptides; Prostatic Neoplasms; Radiotherapy; Retrospective Studies; Suicide; Tosyl Compounds

Prostate cancer patients who receive androgen deprivation therapy (ADT) often experience many physical and psychological side effects. ADT may be associated with increased risk for depression, but the relationship between ADT and depression is not fully understood. This study used a longitudinal design to assess depressive symptomatology in patients receiving ADT compared with two groups of matched controls.. Participants were men initiating ADT treatment (ADT+ group; n = 61) and their matched controls: prostate cancer patients treated with radical prostatectomy (ADT- group; n = 61), and no-cancer controls (CA- group; n = 61). Depressive symptomatology was assessed using the Center for Epidemiological Studies Depression Scale at ADT initiation and again 6 months later. Differences in depressive symptomatology and rates of clinically significant depressive symptomatology were analyzed between groups at each time point and within groups over time.. Between baseline and follow-up, ADT+ participants demonstrated increased depressive symptomatology and increased rates of clinically significant depressive symptomatology (ps < 0.05). ADT+ participants also reported greater depressive symptomatology than both control groups at follow-up (ps < 0.001). Rates of clinically significant depressive symptomatology were higher in the ADT+ group than the ADT- and CA- groups at both time points (baseline: 28%, 5%, 12%; follow-up: 39%, 9%, 11%).. Findings support the hypothesis that ADT administration yields increases in depression and suggest that the mechanism behind ADT's association with depression should be explored and that prostate cancer patients treated with ADT should receive particular focus in depression screening and intervention.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antidepressive Agents; Antineoplastic Agents, Hormonal; Case-Control Studies; Chemotherapy, Adjuvant; Depression; Depressive Disorder; Goserelin; Humans; Leuprolide; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Risk Factors

Topics: Aged; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Depressive Disorder; Humans; Injections, Intramuscular; Leuprolide; Male; Testosterone

Gonadotropin-releasing hormone (GnRH) agonists are synthetic derivatives of the native decapeptide produced by the hypothalamus. These agents cause a reversible suppression of the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the anterior pituitary gland. With GnRH agonist therapy, there is a resulting loss of endogenous ovarian gonadotropin stimulation and a severe hypo-estrogen state consistent with castrate levels of estrogen. Recently, GnRH agonists such as leuprolide and goserelin have been noted to be effective in treating mild to severe endometriosis. Side effects of these agents are consistent with the physiological effects of ovarian suppression, such as vasomotor instability, vaginal dryness, and headaches. However, despite some reports of emotional lability as an adverse effect of GnRH agonists, it appears that the occasional, rather severe psychiatric consequences of these agents are underappreciated. In this article, we present the case reports of 4 women of reproductive age with no prior psychiatric history who were treated with a GnRH agonist for endometriosis. These women developed symptoms consistent with various psychiatric disorders, including panic disorder and major depression with and without psychotic features. Three of these patients were given sertraline while on GnRH agonist therapy, which improved their mood and anxiety symptoms. Women undergoing GnRH agonist therapy may provide a model with which to investigate mood disorders during the perimenopausal stage of life.

Topics: 1-Naphthylamine; Adult; Antidepressive Agents; Antineoplastic Agents, Hormonal; Anxiety Disorders; Depressive Disorder; Endometriosis; Female; Humans; Leuprolide; Sertraline