PROTOCOL: A cohort study examining the association between mirtazapine and mortality risk in adults with a diagnosis of depression

Joseph, Rebecca M.; Jack, Ruth H; Morriss, Richard; Knaggs, Roger; Hollis, Chris; Hippisley‐Cox, Julia; Coupland, Carol

doi:10.1101/2021.02.08.21250305

Cited by 2 publications

(3 citation statements)

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“…This analysis differed from the original protocol13 in the following ways. First, a 30-day risk carry-over window was used instead of the planned 6 months (included as a sensitivity analysis).…”

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

“…The study protocol, 13 code lists ( https://clinicalcodes.rss.mhs.man.ac.uk ) and statistical code used to prepare and analyse the data ( https://doi.org/10.5281/zenodo.4779024 ) are available online. The study used anonymised data provided under licence by the Clinical Practice Research Datalink (CPRD).…”

Section: Methodsmentioning

confidence: 99%

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Association between mirtazapine use and serious self-harm in people with depression: an active comparator cohort study using UK electronic health records

Joseph

Jack

Morriss

et al. 2022

Evid Based Mental Health

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BackgroundStudies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants.ObjectivesTo compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants as second-line treatments.Design and settingCohort study using anonymised English primary care electronic health records, hospital admission data and mortality data with study window 1 January 2005 to 30 November 2018.Participants24 516 people diagnosed with depression, aged 18–99 years, initially prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine, a different SSRI, amitriptyline or venlafaxine.Main outcome measuresHospitalisation or death due to deliberate self-harm. Age–sex standardised rates were calculated and survival analyses were performed using inverse probability of treatment weighting to account for baseline covariates.ResultsStandardised rates of serious self-harm ranged from 3.8/1000 person-years (amitriptyline) to 14.1/1000 person-years (mirtazapine). After weighting, the risk of serious self-harm did not differ significantly between the mirtazapine group and the SSRI or venlafaxine groups (HRs (95% CI) 1.18 (0.84 to 1.65) and 0.85 (0.51 to 1.41) respectively). The risk was significantly higher in the mirtazapine than the amitriptyline group (3.04 (1.36 to 6.79)) but was attenuated after adjusting for dose.ConclusionsThere was no evidence for a difference in risk between mirtazapine and SSRIs or venlafaxine after accounting for baseline characteristics. The higher risk in the mirtazapine versus the amitriptyline group might reflect residual confounding if amitriptyline is avoided in people considered at risk of self-harm.Clinical implicationsAddressing baseline risk factors and careful monitoring might improve outcomes for people at risk of serious self-harm.

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

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Association between mirtazapine use and serious self-harm in people with depression: an active comparator cohort study using UK electronic health records

Joseph

Jack

Morriss

et al. 2022

Evid Based Mental Health

Self Cite

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The risk of all-cause and cause-specific mortality in people prescribed mirtazapine: an active comparator cohort study using electronic health records

Joseph

Jack

Morriss

et al. 2022

BMC Med

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Background Studies have reported an increased risk of mortality among people prescribed mirtazapine compared to other antidepressants. The study aimed to compare all-cause and cause-specific mortality between adults prescribed mirtazapine or other second-line antidepressants. Methods This cohort study used English primary care electronic medical records, hospital admission records, and mortality data from the Clinical Practice Research Datalink (CPRD), for the period 01 January 2005 to 30 November 2018. It included people aged 18–99 years with depression first prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine (5081), a different SSRI (15,032), amitriptyline (3905), or venlafaxine (1580). Follow-up was from starting to stopping the second antidepressant, with a 6-month wash-out window, censoring at the end of CPRD follow-up or 30 November 2018. Age-sex standardised rates of all-cause mortality and death due to circulatory system disease, cancer, or respiratory system disease were calculated. Survival analyses were performed, accounting for baseline characteristics using inverse probability of treatment weighting. Results The cohort contained 25,598 people (median age 41 years). The mirtazapine group had the highest standardised mortality rate, with an additional 7.8 (95% confidence interval (CI) 5.9–9.7) deaths/1000 person-years compared to the SSRI group. Within 2 years of follow-up, the risk of all-cause mortality was statistically significantly higher in the mirtazapine group than in the SSRI group (weighted hazard ratio (HR) 1.62, 95% CI 1.28–2.06). No significant difference was found between the mirtazapine group and the amitriptyline (HR 1.18, 95% CI 0.85–1.63) or venlafaxine (HR 1.11, 95% CI 0.60–2.05) groups. After 2 years, the risk was significantly higher in the mirtazapine group compared to the SSRI (HR 1.51, 95% CI 1.04–2.19), amitriptyline (HR 2.59, 95% CI 1.38–4.86), and venlafaxine (HR 2.35, 95% CI 1.02–5.44) groups. The risks of death due to cancer (HR 1.74, 95% CI 1.06–2.85) and respiratory system disease (HR 1.72, 95% CI 1.07–2.77) were significantly higher in the mirtazapine than in the SSRI group. Conclusions Mortality was higher in people prescribed mirtazapine than people prescribed a second SSRI, possibly reflecting residual differences in other risk factors between the groups. Identifying these potential health risks when prescribing mirtazapine may help reduce the risk of mortality.

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PROTOCOL: A cohort study examining the association between mirtazapine and mortality risk in adults with a diagnosis of depression

Cited by 2 publications

References 33 publications

Association between mirtazapine use and serious self-harm in people with depression: an active comparator cohort study using UK electronic health records

Association between mirtazapine use and serious self-harm in people with depression: an active comparator cohort study using UK electronic health records

The risk of all-cause and cause-specific mortality in people prescribed mirtazapine: an active comparator cohort study using electronic health records

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