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Cited by 116Treatment of Major DepressionElectroconvulsive Therapy StudiesPsychological Treatments and Disorders

Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment-resistant depression

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Thomas, Samantha J., Shin, Mirae, McInnis, Melvin G., Bostwick, Jolene R.·2015·Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
DOI 10.1002/phar.1576
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Abstract

Treatment‐resistant depression (TRD) is a major health concern. More than 40% of patients treated for major depressive disorder with an appropriate antidepressant dose for an adequate duration fail to respond. Further, approximately half of adults with major depressive disorder fail to achieve sustained remission despite various medication trials. The utilization of monoamine oxidase inhibitors (MAOIs) for the treatment of depression in clinical practice today is low due to their widely known adverse effects, some of which may be life threatening, and the risk for dietary and drug interactions. For these reasons, MAOIs are not recommended to be prescribed along with other antidepressants or certain prescription or nonprescription drugs. Pharmacologic options are limited for individuals with TRD, however, and there is a paucity of data on the efficacy of MAOIs in combination with other antidepressants for the management of TRD. We performed a search of the PubMed database (inception through January 25, 2015) to identify cases that illustrate the potential utility, as well as risks, of combination treatment with MAOIs and other antidepressants for the management of TRD; 18 articles met the criteria for our search. In addition, we performed a retrospective case series by reviewing the medical records of 29 adults treated for depression with an MAOI plus another psychotropic agent (an antidepressant or stimulant medication) between 2003 and 2012 at a large Midwestern teaching hospital. We compared the findings of the published experience with our local experience to allow for more informed decisions regarding pharmacotherapy in patients with TRD. We separated the local experience into two groups: 15 cases with the selective MAO type B inhibitor selegiline combined with medications presumed to increase the risk of serotonin syndrome and 14 cases with nonselective MAOIs (phenelzine and tranylcypromine) combined with other contraindicated medications. Although risks of combination treatment certainly exist with selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, or clomipramine, the current literature supports cautious use of combining MAOIs with other antidepressants in patients with TRD who have failed multiple treatment modalities. In addition, the data from the 29 patients receiving combination therapy with an MAOI and another antidepressant or stimulant medication revealed that 21% improved significantly, with no complications. This case series and literature review suggest that when used under close supervision and under the care of an experienced clinician in psychiatry, combination therapy may be a consideration for the management of TRD in patients not responding to monotherapy or other combinations of antidepressants.

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  • Both methylphenidate-based and amphetamine-based agents are contraindicated in individuals taking an MAO inhibitor (currently or within the preceding 2 weeks) because a hypertensive crisis may result.

    “In fact, both MPH-based agents and AMP-based agents are contraindicated in individuals taking an MAO inhibitor (currently or within the preceding 2 weeks) because a hypertensive crisis may result (240).”

    From The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities (2018) · cites this paper as [240]

    Table 1 (p. 434) lists amphetamines and methylphenidate with hypertensive crisis as a potential reaction to MAOI co-use. But its heading groups contraindicated drugs with drugs recommended for cautious use; the “MAOI plus Stimulants” section describes supervised combination use rather than a categorical contraindication. The paper’s two-week washout recommendation concerns SSRIs/SNRIs, not stimulants. (LLM, conf=0.88)

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Authors
Thomas, S. J., Shin, M., McInnis, M. G., & Bostwick, J. R.
Affiliations
  • Meijer Pharmacy Dewitt Michigan
  • Michigan Medicine (US)
  • University of Michigan (US)
Corresponding author
Bostwick, Jolene R.
ORCID
Venue
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Publisher
Wiley
Published
2015-04
Volume
35
Issue
4
Pages
433-449
ISSN
  • 0277-0008 (ISSN-L)
  • 1875-9114
DOI
10.1002/phar.1576
OpenAlex
W2044138799
Cited by
116
References
3
Citations by year
2026: 5 · 2025: 8 · 2024: 16 · 2023: 12 · 2022: 15 · 2021: 15 · 2020: 12 · 2019: 7 · 2018: 9 · 2017: 5 · 2016: 8 · 2015: 4
FWCI
1.09
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 16 d)
Locations
  • Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy (publishedVersion)
  • PubMed (publishedVersion)
  • Deep Blue (University of Michigan) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
  • Social Sciences › Psychology › Clinical Psychology › Psychological Treatments and Disorders
Keywords
treatment-resistant depression, monoamine oxidase inhibitors, selegiline, phenelzine, tranylcypromine, combination pharmacotherapy, antidepressants, stimulants, serotonin syndrome, drug interactions, adverse drug reactions, major depressive disorder, clomipramine, selective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, dietary restriction
MeSH terms
Contraindications, Central Nervous System Stimulants, Antidepressive Agents, Depression, Major Depressive Disorder, Depressive Disorder, Major, Drug Interactions, Drug Therapy, Combination, Humans, Monoamine Oxidase Inhibitors, Treatment Failure

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