Melatonin treatment of winter depression: a pilot study

doi:10.1016/S0165-1781(97)00128-5

Psychiatry Research

Volume 77, Issue 1, 16 January 1998, Pages 57-61

https://doi.org/10.1016/S0165-1781(97)00128-5 Get rights and content

Abstract

Five patients with winter depression received low doses of melatonin in the afternoon, and five patients received placebo capsules. Melatonin treatment significantly decreased depression ratings compared to placebo. If these findings are replicated in a larger sample with documentation of expected phase shifts, the phase shift hypothesis will be substantially supported.

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Cited by (94)

Antidepressant actions of melatonin and melatonin receptor agonist: Focus on pathophysiology and treatment
2022, Behavioural Brain Research
Citation Excerpt :
Correspondingly, dysfunction of the melatonergic system is involved in depression. The antidepressant effects of exogenous melatonin have been supported by many clinical studies [46–51] (Table 2). Besides, subsequent preclinical studies have reported the relationship between melatonin and depression.
Depression has become one of the most commonly prevalent neuropsychiatric disorders, and the main characteristics of depression are sleep disorders and melatonin secretion disorders caused by circadian rhythm disorders. Abnormal endogenous melatonin alterations can contribute to the occurrence and development of depression. However, molecular mechanisms underlying this abnormality remain ambiguous. The present review summarizes the mechanisms underlying the antidepressant effects of melatonin, which is related to its functions in the regulation of the hypothalamic-pituitary-adrenal axis, inhibition of neuroinflammation, inhibition of oxidative stress, alleviation of autophagy, and upregulation of neurotrophic, promotion of neuroplasticity and upregulation of the levels of neurotransmitters, etc. Also, melatonin receptor agonists, such as agomelatine, ramelteon, piromelatine, tasimelteon, and GW117, have received considerable critical attention and are highly implicated in treating depression and comorbid disorders. This review focuses on melatonin and various melatonin receptor agonists in the pathophysiology and treatment of depression, aiming to provide further insight into the pathogenesis of depression and explore potential targets for novel agent development.
Use of immediate release melatonin in psychiatry: BMI impacts the daily-dose
2021, Encephale
There is a growing interest in psychiatry regarding melatonin use both for its soporific and chronobiotic effects. This study aimed to evaluate factors impacting the daily-dose.
In a university department of psychiatry in Paris (France), we conducted a posteriori naturalistic observational study from April 03, 2017 to January 31, 2018. We assessed links between sociodemographic and clinical characteristics and daily dose of melatonin (the daily-dose of melatonin initiation and the daily-dose at Hospital discharge). A survey of drug interactions was performed regarding metabolic inducers and inhibitors of the cytochrome P450 1A2.
Forty patients were included and treated with immediate-release melatonin. For patients with no history of melatonin use, the initiation dose of was 2 or 4 mg, with no effects of age, weight, BMI, melatonin indication, cause of hospitalization. We found that higher discharge dose was associated with higher BMI (P = 0.036) and more reevaluations of melatonin dose (P = 0.00019). All patients with a moderate inducer (n = 3, here lansoprazole) were significantly more associated with the discontinuation melatonin group (P = 0.002).
The BMI and the number of reevaluations impact the daily dose of melatonin. Two mechanisms may explain that BMI may need higher doses: (i) melatonin diffuses into the fat mass, (ii) the variant 24E on melatonin receptor MT2, more frequent in obese patients, leads to a decrease of the receptor signal.
La mélatonine bénéficie d’un intérêt clinique croissant et est de plus en plus utilisée dans les troubles psychiatriques, tant pour ses effets soporifiques que pour ses effets chronobiotiques. Cette étude a pour objectif d’évaluer les facteurs pouvant avoir un impact sur la dose quotidienne de mélatonine utilisée en psychiatrie.
Dans un département universitaire de psychiatrie à Paris (France), nous avons mené une étude observationnelle pragmatique à posteriori du 03 avril 2017 au 31 janvier 2018. Nous avons évalué les liens entre les caractéristiques sociodémographiques et cliniques et la dose journalière de mélatonine (dose d’initiation et dose de sortie d’hospitalisation). De plus, une étude des interactions médicamenteuses a été réalisée concernant les inducteurs métaboliques et les inhibiteurs du cytochrome P450 1A2.
Quarante patients ont été inclus et traités avec de la mélatonine à libération immédiate. Pour les patients sans antécédent d’utilisation de mélatonine, les doses d’initiation étaient soit 2 ou 4 mg. L’âge, le poids, l’Indice de Masse Corporelle (IMC), l’indication de la mélatonine et la cause de l’hospitalisation n’avaient aucune influence retrouvée sur la dose d’initiation de mélatonine. Au cours de l’hospitalisation, la période médiane entre chaque réévaluation de dose de mélatonine était de 4,5 jours. En sortie d’hospitalisation, la dose médiane de mélatonine était de 4 mg. Nous avons constaté que l’utilisation de doses élevées de mélatonine était associée à un IMC plus élevé (p = 0,036) et un nombre de réévaluations des doses de mélatonine au cours de l’hospitalisation plus élevé (p = 0,00019). Tous les patients ayant un inducteur modéré (n = 3, ici le lansoprazole) ont été significativement plus associés au groupe ayant cessé de prendre de la mélatonine (p = 0,002).
L’IMC et le nombre de réévaluations semblent avoir un impact sur la dose quotidienne de mélatonine. Deux mécanismes peuvent être évoqués pour expliquer l’utilisation de dose plus élevée chez les personnes avec un IMC plus élevée: (i) la mélatonine se diffuse dans la masse graisseuse, (ii) le variant 24E du récepteur de la mélatonine MT2, plus fréquente chez les patients obèses, entraîne une diminution du signal du récepteur.
Biological rhythms and chronotherapeutics in depression
2021, Progress in Neuro-Psychopharmacology and Biological Psychiatry
Depressive syndromes are frequent and heterogeneous brain conditions with more than 90% of patients suffering from sleep complaints. Better characterizing this “sleep” domain may allow to both better treat acute episodes with existing chronotherapeutics, but also to prevent the manifestation or recurrences of mood disorders. This work aims to i) review theoretical and fundamental data of chronotherapeutics, and ii) provide practical recommendations. Light therapy (LT) can be used as a first-line monotherapy of moderate to severe depression of all subtypes. LT can be also used as a combination with antidepressant to maximize patients’ response rates, which has a clear superiority to antidepressant alone. Sleep deprivation (SD) is a rapid and powerful chronotherapeutic with antidepressant responses within hours in 45-60% of patients with unipolar or bipolar depression. Different strategies should be combined to stabilize the SD antidepressant effect, including concomitant medications, repeated SD, combination with sleep phase advance and/or LT (triple chronotherapy). Melatonin treatment is of interest in remitted patients with mood disorder to prevent relapses or recurrences, if a complaint of insomnia, poor sleep quality or phase delay syndrome is associated. During the acute phase, melatonin could be used as an adjuvant treatment for symptoms of insomnia associated with depression. The cognitive behavioral therapy for insomnia (CBT-I) can be recommend to treat insomnia during euthymic phases. The Interpersonal and social rhythm therapy (IPSRT) is indicated for the acute treatment of bipolar depression and for the prevention of mood episodes. Chronotherapeutics should always be associated with behavioral measures for healthy sleep.
Primary role for melatonin MT<inf>2</inf> receptors in the regulation of anhedonia and circadian temperature rhythm
2021, European Neuropsychopharmacology
Citation Excerpt :
Indeed, melatonin results in an effective option for individuals with depressive symptomatology comorbid with circadian rhythm sleep disruption . Furthermore, the antidepressant effectiveness of melatonin in animal models of depression has been associated to its chronobiotic properties (Barden et al., 2005; Crupi et al., 2010; Detanico et al., 2009; Estrada-Reyes et al., 2018; Jean-Louis et al., 1998; Lanfumey et al., 2013; Lewy et al., 1998; Nagy et al., 2015; Papp et al., 2003; Serfaty et al., 2010; Rahman et al., 2010). Through binding to the two G-protein coupled melatonin receptors, MT1 and MT2, in the suprachiasmatic nucleus (SCN) of the hypothalamus, melatonin controls the phase shift of relevant circadian rhythms (Nagy et al., 2015).
Circadian rhythms disturbance is widely observable in patients with major depression (MD) and is also associated with depression vulnerability. Of them, disturbed melatonin secretion rhythm is particularly relevant to MD and is strongly phase-locked to core body temperature (CBT) rhythm.
Here we aim to study the specific role of each melatonin receptor (MT₁ and MT₂) subtype in melatonin regulation of circadian CBT and its possible relationship with depressive-like behaviors.
MT₁-/- , MT₂-/- and WT (C57BL/6) mice were used. Anhedonia, using the sucrose intake test, circadian CBT, environmental place preference (EPP) conditioning and vulnerability to chronic social defeat stress (CSDS) procedure were studied. Moreover, the antidepressant effects of reboxetine (15 mg/kg/day, i.p.) for three weeks or ketamine (15 mg/kg i.p. every four days, 4 doses in total) were studied. Further, exposure to ultra-mild stress induced by individual housing for several weeks was also studied in these mice.
MT₂-/- mice showed anhedonia and lower CBT compared to WT and MT₁-/-. In addition, while reward exposure raised nocturnal CBT in WT this increase did not take place in MT₂-/- mice. Further, MT₂-/- mice showed an enhanced vulnerability to stress-induced anhedonia and social avoidance as well as an impaired acquisition of novelty seeking behavior. Both reboxetine and ketamine reverted anhedonia and induced a clear anti-helpless behavior in the tail suspension test (TST). Reboxetine raised CBT in mice and reverted ultra-mild stress-induced anhedonia.
Our findings show a primary role for MT₂ receptors in the regulation of circadian CBT as well as anhedonia and suggest that these receptors could be involved in depressive disorders associated to disturbed melatonin function.
Melatonin attenuated the behavioral despair induced by acute neurogenic stress through blockade of N-methyl D-aspartate receptors in mice
2021, Heliyon
Citation Excerpt :
The link between melatonin and depressive disorders such as seasonal affective disorder (SAD) has received attention (Kaminski-Hartenthaler et al., 2015; Lewy et al., 1998). The antidepressant effects of melatonin have been supported by many clinical studies (Hickie and Rogers, 2011; Lewy et al., 1998). Also, antidepressant effects of melatonin have been reported in the FST when it was acutely administered (Mantovani et al., 2003).
It has been well documented that administration of melatonin could reveal antidepressant-like effect in rodents. However, the protective effect of melatonin on stress-induced depression/anxiety and its underlying mechanism is yet to be understood. In this regard, in the current study, acute foot-shock stress (FSS) was used to evaluate the antidepressant-like effect of melatonin on neurogenic stress-induced depression in mice. Behavioral evaluation was done by using the forced swimming test (FST) and Open-field test (OFT). Melatonin, MK-801, and ketamine (NMDA receptor antagonists), and NMDA (NMDA receptor agonist) were used to elucidate any association between melatonin and NMDA pathway in behavioral despair induced by acute-FSS. Applying acute-FSS to mice significantly induced depressant-like behavior in FST without any significant impact on locomotor activity in the OFT. We observed that melatonin (dose-dependently) significantly improved the depressant-like effect of FSS, but it did not impact the locomotion in animals. Acute injection of MK-801 at sub-effective doses (0.01 mg/kg) or ketamine (0.1 mg/kg) potentiated the antidepressant-like effect of a sub-effective dose of melatonin. However, the sub-effective dose of NMDA (30 mg/kg) abolished the protective effect of melatonin on the behavioral profile of stressed animals. Our results could reflect the antidepressant-like effect of melatonin on neurogenic stress-induced depressive behaviors in mice. Also, our results showed that NMDA receptors could be involved in the antidepressant-like effect of melatonin.
The use of melatonin in adult psychiatric disorders: Expert recommendations by the French institute of medical research on sleep (SFRMS)
2019, Encephale
Melatonin is a hormone secreted by the pineal gland at night. This hormone has many physiological functions, the main one being to synchronise individuals’ biological rhythms. Exogenous melatonin has the same chronobiotic action, even at small doses (0.125 mg). In addition, a sleep-inducing (soporific) action appears to occur in a dose-effect relationship, i.e. as the dose increases. In psychiatric disorders, these two effects could have interesting applications in clinical practice. The French institute of medical research on sleep (SFRMS) appointed a group of experts to conduct a consensus conference to study the indications of melatonin and the conditions of its prescription. An account of the conclusions on adult psychiatric disorders (presented orally at the Congress on Sleep in Marseille, 23 November 2017) is given here. Exogenous melatonin proves to be useful among patients with a stabilized psychiatric disorder or in remission, to prevent relapse in case of associated complaints of insomnia, poor quality sleep or delayed sleep phase syndrome. During acute phases, melatonin could be used as an adjuvant treatment when there are insomnia symptoms, in mood disorders (bipolar disorder, major depressive disorder, seasonal affective disorder), in attention deficit hyperactivity disorder (ADHD), in peri-surgical anxiety and in schizophrenia. In somatoform disorders, melatonin is a possible treatment for painful symptoms in fibromyalgia, irritable bowel syndrome, functional dyspeptic syndrome and temporomandibular joint dysfunction.
La mélatonine est une hormone sécrétée par la glande pinéale la nuit. Cette hormone possède plusieurs fonctions physiologiques dont la principale est celle de synchroniser les rythmes biologiques d’un individu. La mélatonine exogène exerce cette même action « chronobiotique » dès l’administration de faibles doses (0,125 mg). De plus, une action promotrice du sommeil (dite « soporifique ») apparaît en relation dose-effet, c’est-à-dire avec l’augmentation de dose. Dans les troubles psychiatriques, ces deux actions pourraient avoir des effets intéressants en pratique clinique. La Société Française de Recherche et Médecine du Sommeil (SFRMS) a mandaté un groupe d’experts au sein d’une conférence de consensus qui a consacré son travail aux indications de la mélatonine et aux conditions de sa prescription. Nous rendons compte ici des conclusions concernant les troubles psychiatriques de l’adulte (rendues oralement au Congrès du Sommeil, Marseille, 23 novembre 2017). La mélatonine exogène présente un intérêt chez les patients souffrant d’un trouble psychiatrique stabilisé ou en rémission afin de prévenir la rechute quand une plainte d’insomnie, de mauvaise qualité du sommeil ou de syndrome de retard de phase, est associée. Au cours des phases aiguës, la mélatonine pourrait être utilisée comme un traitement adjuvant lorsqu’il existe des symptômes d’insomnie dans les troubles thymiques (trouble bipolaire, trouble dépressif, trouble affectif saisonnier), dans le TDAH, dans l’anxiété péri-opératoire, et dans la schizophrénie. Dans les troubles somatoformes, la mélatonine est un traitement possible des symptômes douloureux de la fibromyalgie, du syndrome de l’intestin irritable, du syndrome dyspeptique fonctionnel, et du trouble temporo mandibulaire.

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Brief reportMelatonin treatment of winter depression: a pilot study

Abstract

Biological Psychiatry

Biological Psychiatry

Journal of Psychiatric Research

Light therapy for winter depression is more than a placebo

Society for Light Treatment and Biological Rhythms Abstracts

Development of a rating scale for primary depressive illness

British Journal of the Society for Clinical Psychology

Phototherapy for seasonal affective disorder: a blind comparison of three different schedules

American Journal of Psychiatry

Exogenous melatonin's phase shifting effects on the endogenous melatonin profile in sighted humans: a brief review and critique of the literature

Journal of Biological Rhythms

Melatonin shifts circadian rhythms according to a phase-response curve

Chronobiology International

Brief report
Melatonin treatment of winter depression: a pilot study