Double-blind, placebo-controlled study of single-dose metergoline in depressed patients with seasonal affective disorder.

A role for serotonin in season affective disorder (SAD) has been explored with a variety of serotonergic pharmacologic agents. The authors initially hypothesized that metergoline, a nonspecific serotonin antagonist, would exacerbate depressive symptoms. In a small, open-label pilot study, the authors observed the opposite effect. They decided to follow up on this finding with this formal study. The study followed a double-blind, randomized cross-over design. Sixteen untreated, depressed patients with SAD received single oral doses of metergoline 8 mg and of placebo, spaced 1 week apart. Fourteen patients were restudied after 2 weeks of light treatment. Depression ratings using the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version were performed at baseline and at 3 and 6 days after each intervention. These data were analyzed by baseline-corrected repeated measures with analysis of variance. In the off-lights condition, severity of depression was diminished after metergoline compared with placebo administration (p = 0.001). Patient daily self-ratings suggested that the peak effect occurred 2 to 4 days after study drug administration. In contrast, after 2 weeks of treatment with bright artificial light, metergoline did not demonstrate a significant effect on mood. These data suggest that single doses of metergoline may have antidepressant effects that last several days. Possible mechanisms include 5-hydroxytryptamine(2) receptor downregulation and dopamine agonism.

[Plasma prolactin concentration and the effect of metergoline in pseudopregnant Afghan hounds]. / Plasma-prolactineconcentraties en het effect van metergoline bij pseudogravide Afghaanse windhonden.

The effects of metergoline, a 5-hydroxytryptamine (serotinin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-psueodopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentration of prolactine in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

Severe postpartum hypertension and reversible cerebral angiopathy associated with ergot derivative (methergoline) administration.

A 36-year-old woman (gravida 2, para 2) delivered a healthy child by cesarean section at the 37th week of an unremarkable gestation. Blood pressure remained within normal range throughout the pregnancy, surgery, and for the 9 following days. On day 10, about 36 hours after the initiation of oral methergoline to suppress lactation, the patient complained of severe posterior headache, flashing scotomata, hypertension, tonico-clonic seizures and then homonymous left hemianopsia and hemiparesis. Blood pressure monitoring confirmed intermittent and severe hypertension. Angiography demonstrated diffuse narrowing of the small and medium cerebral arteries. Transcranial Doppler ultrasound examination disclosed a bilateral increase in mean flow velocity. Progressive normalization of blood pressure, obtained with labetalol and oral clonidine, was accompanied by amelioration of the neurological deficits until a complete recovery and normalization of transcranial Doppler flow velocity occurred. This case provides further evidences that hypertension might play a major pathogenetic role in reversible cerebral angiopathy. Some ergot derivatives (including methergoline) might trigger the initial rise in blood pressure.

Plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and the effect of metergoline.

The effect of metergoline, a 5-hydroxytryptamine (serotonin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-pseudopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentrations of prolactin in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

[The treatment of pseudopregnancy in the bitch with prolactin inhibitors metergoline and bromocriptine]. / Untersuchung zur Behandlung der Scheinträchtigkeit der Hündin mit den Prolaktinhemmern Metergolin und Bromocryptin.

In the present study, the prolactin inhibitor Metergoline was compared with Bromocriptine and tested against a placebo in 63 pseudogravid bitches. Bromocriptine has already been tested successfully in numerous investigations on the therapy of canine pseudogravidity, but--probably because of its high price and vomitus as a frequent side effect--it has not been really introduced as a therapeutical device in canine practice. It can be deduced from the results presented herein that prolactin is essential for maintaining the pseudogravidity, but keeping up the lactation process--especially galactopoiesis--can probably not be ascribed solely to prolactin. However, prolactin definitely plays an essential role in the hormonal scenario, the detailed regulating mechanisms of which are not known until today. Thus, no statistically convincing therapy outcome could be achieved by the prolactin inhibitors compared to the placebo group. A tendency towards earlier regression of the symptoms "mammogenesis", "behavioural change" and "galactorrhea" was however present in the treated animals. A striking difference was the much more lively behaviour of the bitches with 53% being more lively in the Metergoline group, 37% in the Bromocriptine and 10% in the placebo group. There were also clear differences in the compatibility of the drugs; in the Bromocriptine group, 30% of the animals vomited, in the Metergoline only 6.3%. This however did not lead to termination of the therapy in any case. In two cases of the Metergoline group (6.3%), the medication was ended due to extreme restlessness.

[Puerperal inhibition of lactation with metergoline or bromocriptine]. / Die puerperale Laktationshemmung mit Metergolin oder Bromocriptin.

In a controlled, randomised, prospective, clinical study, the effect of prolactin suppression and clinical course of the lactation suppressors Bromocriptine and Metergoline were investigated. During 7 months 150 patients were studied. 81 of those patients, who did not nurse, were treated by Bromocriptine (primary lactation suppression: n = 62, secondary suppression: n = 19) and 69 of the patients were treated by Metergoline (primary suppression: n = 54, secondary suppression: n = 15). The drugs were administrated orally to all subjects, dosed 2 x 2.5 mg/d of Bromocriptine for 14 days and 3 x 4 mg/d of Metergoline for 10 days, starting in average after 13 hours. Puerperal suppression of prolactine were compared with randomised breast feeding subjects (n = 30). In Bromocriptine treated women the average plasma prolactin level decreased from 78.4 +/- 22 ng/ml to 17.0 +/- 3.3 ng/ml during five days of treatment. In Metergoline treated women the plasma prolactin level decreased from 129.7 +/- 15.1 ng/ml to 56.9 +/- 10.0 ng/ml during the first days of treatment. Prolactin level of breast feeding subjects decreased from 233.6 +/- 21.4 ng/ml to 185.8 +/- 23.7 ng/ml during the same period (p < 0.05). There is no statistical significancy of clinical difference of both drugs, but a statistical trend was seen. With Bromocriptine treated women were suppressed efficiently in 71 of 81 cases, 10 refused. Refusals were divided in two quality levels, level I with subjects with moderate complaints and little puerperal lactation, level II with subjects with considerable complaints including strong puerperal lactation. With Metergoline suppressed women, treatment was efficiently in 51 of 69 cases, but refusals of level I were observed in 11 cases and refusals of level II were observed in 7 cases. The results show that Bromocriptine and Metergoline are effective on suppression of lactation. Under the current drug dose of Metergoline an advantage of Bromocriptine were observed. Only further studies could investigate, whether an adaptation of drug dose would improve the clinical efficiency of Metergoline.

Treatment of hyperprolactinemic amenorrhea with Metergoline.

The ergoline derivative, Metergoline, in a dosage of 4 to 24 mg/day, was administered for one to eight months to 42 patients with hyperprolactinemic amenorrhea. Mean serum prolactin (PRL) concentrations before treatment were 91.2 ng/mL in the patients with functional hyperprolactinemia (N = 29) and 256.9 ng/mL in the patients with pituitary tumor (N = 13). Within four weeks, Metergoline treatment reduced these PRL concentrations to 39.5 ng/mL and 82.9 ng/mL, respectively. In this study Metergoline treatment resulted in restoration of menstruation in a total of 37 patients; 28 patients ovulated, and eight became pregnant. It is considerably more effective in functional hyperprolactinemia than in hyperprolactinemia caused by adenoma.

[Clinical experiences with the prolactin-inhibiting serotonin antagonist metergoline]. / Klinische Erfahrungen mit dem prolaktininhibierenden Serotoninantagonisten Metergolin.

20 puerperal women who did not wish to breast feed their infants were treated with the serotonin antagonist metergoline. In 19 cases effective suppression of puerperal lactation was achieved by the administration of metergoline without the side effects or signs of intolerance. Of 9 women with hyperprolactinaemic amenorrhoea treated with metergoline the raised prolactin level was lowered, followed by menstruation in 7 patients. Ovulation even occurred in 5 of these women. One patient had to discontinue therapy due to intolerance. in normoprolactinaemic amenorrhoea regular menstruation reappeared in 4 out of 5 women; 2 patients even ovulated.

Treatment of hyperprolactinaemia with metergoline for periods up to 5 years: clinical and biological tolerability.

Forty patients with hyperprolactinaemia were treated with metergoline (8 to 12 mg/day) for periods up to 5 years. Analysis of the results of clinical and biological tolerability showed that treatment was generally well tolerated and although 28 patients complained of drug-related side-effects of various kinds, principally nausea, these were usually mild, present at the beginning of treatment and disappeared spontaneously in spite of continued metergoline administration over a prolonged period. No patient stopped treatment because of side-effects. Laboratory parameters also stayed within normal levels and there was no evidence of any alterations in the ECG. It is concluded, therefore, that metergoline is a well-tolerated as well as an effective ergolinic compound for use in those patients in whom prolonged treatment with a prolactin-lowering drug is considered necessary.

Metergoline versus bromocriptine in the prevention of puerperal lactation. A double-blind clinical trial.

In a double blind study of the prevention of puerperal lactation, the clinical efficacy of two antiprolactin drugs was compared: metergoline 4 mg tid and bromocriptine 2.5 mg bid were both given for 7 days. An additional 7 days of treatment was administered to 16 patients in whom mammary activity was still present or appeared in the following 3 days. The first 7 day period of treatment was effective in 16/20 women receiving metergoline and in 7/20 on bromocriptine (p less than 0.02); the second period of treatment was effective in all remaining patients. These data indicate that metergoline acts rapidly to arrest puerperal lactation, possibly by a mechanism different from that of bromocriptine.