Effect of mirtazapine versus selective serotonin reuptake inhibitors on benzodiazepine use in patients with major depressive disorder: a pragmatic, multicenter, open-label, randomized, active-controlled, 24-week trial

Hashimoto, Tasuku; Shiina, Akihiro; Hasegawa, Tadashi; Kimura, Hiroshi; Oda, Yasunori; Niitsu, Tomihisa; Ishikawa, Masatomo; Tachibana, Masumi; Muneoka, Katsumasa; Matsuki, Satoshi; Nakazato, Michiko; Iyo, Masaomi

doi:10.1186/s12991-016-0115-1

Cited by 10 publications

(7 citation statements)

References 44 publications

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“…We found similar results: in animals dosed with 30 mg mirtazapine, anxiety-like (as measured in the EPM test, OFT and the LDT) and depression-like behaviors (according to the FST) decreased after 15 days of treatment. Studies elsewhere have indicated that mirtazapine exerts rapid antidepressant effects compared with drugs such as the SSRIs (Hashimoto et al, 2016;Tsutsumi et al, 2016). Again, our results were similar -after only 15 days of treatment, we noted a decrease in depression-and anxiety-like behaviors.…”

Section: -supporting

confidence: 85%

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Mirtazapine attenuates anxiety- and depression-like behaviors in rats during cocaine withdrawal

Méndez

Salazar-Juárez

2019

J Psychopharmacol

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Background: Anxiety and depression, key symptoms of the cocaine withdrawal syndrome in human addicts, are considered the main factors that precipitate relapse in chronic cocaine addiction. Preclinical studies have found that rodents exposed to different withdrawal periods show an increase in anxiety and depressive-like behavior. Mirtazapine – a tetracyclic medication – is used primarily to treat depression and, sometimes, anxiety. It has also successfully improved withdrawal symptoms in drug-dependent patients. Aim: This study sought to determine whether chronic dosing of mirtazapine during cocaine withdrawal reduced depression- and anxiety-like behaviors that characterize cocaine withdrawal in animals. Methods: Cocaine pre-treated Wistar rats were subjected to a 60-day cocaine withdrawal period during which depression- and anxiety-like behaviors were evaluated in open field tests (OFT), the elevated plus-maze (EPM), the light–dark box test (LDT), the forced swimming test (FST) and spontaneous locomotor activity (SLA). Results: We found that chronic dosing with different doses of mirtazapine (30 and 60 mg/kg) decreased depression- and anxiety-like behaviors induced by different doses of cocaine (10, 20 and 40 mg/kg) during the 60-day cocaine withdrawal. Interpretation: Our results suggest that the pharmacological effect of mirtazapine on its target sites of action (α2-adrenergic and 5-HT2A and 5-HT3 receptors) within the brain may improve depression- and anxiety-like behaviors for long periods. Conclusion: Therefore, the findings support the use of mirtazapine as a potentially effective therapy to reduce anxiety and depressive-like behavior during cocaine withdrawal.

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Section: -supporting

confidence: 85%

“…Mirtazapine, a tetracyclic antidepressant, is used primarily to treat depression, though it is also sometimes used for anxiety or sleeplessness and other indications (de Boer, 1995(de Boer, , 1996Hashimoto et al, 2016;Tsutsumi et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Mirtazapine attenuates anxiety- and depression-like behaviors in rats during cocaine withdrawal

Méndez

Salazar-Juárez

2019

J Psychopharmacol

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“…Therefore, for the depressed patients with clinically significant insomnia, a treatment with a sedative antidepressant is usually more recommended [ 19 ]. It was recently shown that such treatment significantly reduces the need to use benzodiazepines in patients with MDD [ 20 •]. Such an approach, combination treatment with benzodiazepines and SSRI/SNRI is often necessary to reduce anxiety and insomnia as early as in the first week of treatment.…”

Section: Effects On Antidepressants On Sleepmentioning

confidence: 99%

Effects of Antidepressants on Sleep

Wichniak

Wierzbicka

Walęcka

et al. 2017

Curr Psychiatry Rep

361

230

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Purpose of ReviewThe aim of this review article was to summarize recent publications on effects of antidepressants on sleep and to show that these effects not only depend on the kind of antidepressant drugs but are also related to the dose, the time of drug administration, and the duration of the treatment.Recent FindingsComplaints of disrupted sleep are very common in patients suffering from depression, and they are listed among diagnostic criteria for this disorder. Moreover, midnocturnal insomnia is the most frequent residual symptom of depression. Thus, all antidepressants should normalize sleep. However, at least in short-term treatment, many antidepressants with so-called activating effects (e.g. fluoxetine, venlafaxine) may disrupt sleep, while others with sedative properties (e.g., doxepin, mirtazapine, trazodone) rapidly improve sleep, but may cause problems in long-term treatment due to oversedation.For sleep-promoting action, the best effects can frequently be achieved with a very low dose, administered early enough before bedtime and importantly, always as a part of more complex interventions based on the cognitive-behavioral protocol to treat insomnia (CBT-I).SummaryFor successful treatment of depression, it is necessary to understand the effects of antidepressants on sleep. Each physician should also be aware that some antidepressants may worsen or induce primary sleep disorders like restless legs syndrome, sleep bruxism, REM sleep behavior disorder, nightmares, and sleep apnea, which may result from an antidepressant-induced weight gain.

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“…Although it is very common for the depressed patient to be prescribed hypnotics or anxiolytics with antidepressants, we did not take this treatment into account in our analysis. However, some studies showed that mirtazapine decreased the use of hypnotics significantly . Therefore, the cost‐effectiveness of mirtazapine might improve further if that impact is considered.…”

Section: Discussionmentioning

confidence: 99%

“…However, some studies showed that mirtazapine decreased the use of hypnotics significantly. 44,45 Therefore, the cost-effectiveness of mirtazapine might improve further if that impact is considered.…”

Section: Comparison Of Icers Between Observational Pointsmentioning

confidence: 99%

Does the rapid response of an antidepressant contribute to better cost‐effectiveness? Comparison between mirtazapine and SSRIs for first‐line treatment of depression in Japan

Sado

Wada

Ninomiya

et al. 2019

Psychiatry Clin Neurosci

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Aim Previous studies indicate that mirtazapine is unique in its quick responsiveness compared to other antidepressants. Although some other studies have evaluated its cost‐effectiveness, they have not considered its early stage remission rate. The aim of this study was to address this research gap by using precise clinical data to evaluate the cost‐effectiveness of mirtazapine in Japan. Methods We developed a Markov model to reflect the week‐by‐week transition probabilities. The Markov cycle was set as 1 week. While our clinical parameters were obtained largely from existing meta‐analyses, cost data were derived from government reports. Cost‐effectiveness was evaluated by incremental cost‐effectiveness ratios (ICERs) per quality‐adjusted life year estimated based on the probability sensitivity analyses. The ICERs were estimated at 2, 8, 26, and 52 weeks. Results In severe depression, the ICERs ranged between JPY 872 153 and 1 772 723. The probability of mirtazapine being cost‐effective ranged from 0.75 to 0.99 when the ICER threshold was JPY 5 000 000. In moderate depression, the ICERs ranged between JPY 2 356 499 and 4 770 145. The probability of mirtazapine being cost‐effective ranged from 0.55 to 0.83 when the ICER threshold was JPY 5 000 000. Conclusion When considering the early stage efficacy of mirtazapine, it appeared to be cost‐effective compared to selective serotonin reuptake inhibitors, especially for severe depression and in the early stage treatment in the Japanese setting. However, our study has some limitations. First, mirtazapine is compared with batched selective serotonin reuptake inhibitors rather than individual ones. Second, we did not consider antidepressant combination therapy as treatment options.

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Effect of mirtazapine versus selective serotonin reuptake inhibitors on benzodiazepine use in patients with major depressive disorder: a pragmatic, multicenter, open-label, randomized, active-controlled, 24-week trial

Cited by 10 publications

References 44 publications

Mirtazapine attenuates anxiety- and depression-like behaviors in rats during cocaine withdrawal

Mirtazapine attenuates anxiety- and depression-like behaviors in rats during cocaine withdrawal

Effects of Antidepressants on Sleep

Does the rapid response of an antidepressant contribute to better cost‐effectiveness? Comparison between mirtazapine and SSRIs for first‐line treatment of depression in Japan

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