You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.


Can Certain Medications Delay Treatment Response for Depression?

  • Authors: News Author: Batya Swift Yasgur, MA, LSW; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 7/28/2023
  • Valid for credit through: 7/28/2024, 11:59 PM EST
Start Activity

  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0 contact hours are in the area of pharmacology)

    Pharmacists - 0.25 Knowledge-based ACPE (0.025 CEUs)

    Physician Assistant - 0.25 AAPA hour(s) of Category I credit

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for primary care clinicians, psychiatrists, nurses/nurse practitioners, pharmacists, physician assistants, and other clinicians who care for adults with depression.

The goal of this activity is for the healthcare team to be better able to analyze how the use of drugs with potential depressive symptom side effects (PDSS) can affect symptoms of depression among adults treated for depression.

Upon completion of this activity, participants will:

  • Assess risk factors for treatment-resistant depression
  • Analyze how the use of drugs with PDSS can affect symptoms of depression among adults treated for depression
  • Outline implications for the healthcare team


Medscape, LLC requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.

News Author

  • Batya Swift Yasgur, MA, LSW

    Freelance writer, Medscape


    Batya Swift Yasgur, MA, LSW, has no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine


    Charles P. Vega, MD, has the following relevant financial relationships:
    Consultant or advisor for: Boehringer Ingelheim Pharmaceuticals, Inc.; GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Editor/Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Nurse Planner

  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Leigh Schmidt, MSN, RN, CNE, CHCP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.

Accreditation Statements


Interprofessional Continuing Education

In support of improving patient care, Medscape, LLC is jointly accredited with commendation by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.


This activity was planned by and for the healthcare team, and learners will receive 0.25 Interprofessional Continuing Education (IPCE) credit for learning and change.

    For Physicians

  • Medscape, LLC designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 0.25 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Aggregate participant data will be shared with commercial supporters of this activity.

    College of Family Physicians of Canada Mainpro+® participants may claim certified credits for any AMA PRA Category 1 credit(s)™, up to a maximum of 50 credits per five-year cycle. Any additional credits are eligible as non-certified credits. College of Family Physicians of Canada (CFPC) members must log into Mainpro+® to claim this activity.

    Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME’s “CME in Support of MOC” program in Section 2 of the Royal College’s MOC Program.

    Contact This Provider

    For Nurses

  • Awarded 0.25 contact hour(s) of nursing continuing professional development for RNs and APNs; 0.00 contact hours are in the area of pharmacology.

    Contact This Provider

    For Pharmacists

  • Medscape designates this continuing education activity for 0.25 contact hour(s) (0.025 CEUs) (Universal Activity Number: JA0007105-0000-23-291-H01-P).

    Contact This Provider

  • For Physician Assistants

    Medscape, LLC has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.25 AAPA Category 1 CME credits. Approval is valid until 07/28/2024. PAs should only claim credit commensurate with the extent of their participation.

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 75% on the post-test.

Follow these steps to earn CME/CE credit*:

  1. Read the target audience, learning objectives, and author disclosures.
  2. Study the educational content online or printed out.
  3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. We encourage you to complete the Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates from the CME/CE Tracker.

*The credit that you receive is based on your user profile.


Can Certain Medications Delay Treatment Response for Depression?

Authors: News Author: Batya Swift Yasgur, MA, LSW; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 7/28/2023

Valid for credit through: 7/28/2024, 11:59 PM EST


Clinical Context

Treatment-resistant depression (TRD) is generally defined as the failure to improve after trials of at least 2 antidepressant drugs from different classes, provided that the dosage was adequate and the treatment period was at least 4 weeks with each drug. The authors of the current study suggest that TRD can occur in approximately 30% of cases of depression. A previous study by Rizvi and colleagues focused on the prevalence of TRD in primary care practices in Canada and explored risk factors for TRD as well. The research was published in the July 2014 issue of the Canadian Journal of Psychiatry.[1]

A total of 135 primary care physicians completed 1212 case reports on patients with depression. The prevalence of TRD was 21.7%. Patient sex and race/ethnicity did not affect the risk for TRD; however, patients with TRD were slightly older compared with patients without TRD, and patients who were unemployed or disabled also had higher rates of TRD.

Several comorbid illnesses also affected the risk for TRD. In particular, sleep disorders and chronic pain were associated with higher rates of TRD. Type 2 diabetes, cardiovascular disease, chronic obstructive pulmonary disease, and hepatitis also were associated with higher rates of TRD, but arthritis, asthma, cancer, chronic kidney disease, peripheral vascular disease, and osteoporosis were not.

Chronic health conditions contribute to TRD, and their associated treatment can as well. The current study by Mojtabai and colleagues evaluates how the use of medications with potential depressive symptom side effects (PDSS) affects the treatment of depression.

Study Synopsis and Perspective

Patients with TRD may be taking other medications with adverse effects (AEs) that interfere with antidepressant efficacy.

Investigators studied more than 800 patients who were taking antidepressants for major depressive disorder (MDD) and found that close to two-thirds were taking at least 1 nonpsychiatric medication with PDSS, more than 30% were taking 2 or more such medications, and 20% were taking at least 3 such medications.

These medications, which included antihypertensive medications and corticosteroids, among others, were associated with higher odds of moderate to severe depressive symptoms compared with medications without PDSS.

"When evaluating the reasons for inadequate response to treatment for depression, clinicians should consider whether their patient is also receiving a nonpsychiatric medication with a potential for depressive symptom side effects," study investigator Mark Olfson, MD, MPH, Elizabeth K. Dollard professor of psychiatry, medicine, and law and professor of epidemiology, Columbia University Irving Medical Center, New York, New York, told Medscape Medical News.

The study was published May 24 in The Journal of Clinical Psychiatry.[2]

Previous Research Limited

"In earlier research, we found that people who were taking medications with a potential to cause depressive symptom side effects were at increased risk of depression, especially those adults who were taking more than one of these medications," said Olfson.

This finding led Olfson and his team to "wonder whether the risks of depressive symptoms associated with these medications extended to people who were being actively treated with antidepressants for depression."

To investigate, they turned to the National Health and Nutrition Examination Survey (NHANES): a nationally representative cross-sectional survey of the US general population.

The study was based on the 2013-2014, 2015-2016, and 2017-2018 waves and included 885 adults who reported using antidepressant medications for 6 weeks or longer for depression and whose depression could be ascertained.

Researchers identified prescription medications with PDSS through Micromedex, whose accuracy is "established" and primarily based on the FDA-labeled AEs.

The analysis did not include non-antidepressant psychiatric medications and medications for Alzheimer disease or substance use disorders.

Antidepressant-treated MDD was defined as taking an antidepressant for MDD for 6 or more weeks. Investigators ascertained depressive symptoms using the 9-item Patient Health Questionnaire (PHQ-9) with a score of less than 5 representing no/minimal depressive symptoms and a score of 10 or higher indicating moderate/severe symptoms.

Other variables included self-reported sex; age; race/ethnicity; income; education; health insurance; and common chronic medical conditions, such as hypertension, arthritis, lung disease, diabetes mellitus, thyroid disease, cancer, heart disease, liver disease, stroke, and congestive heart failure.

Recovery Interrupted

Of the patients in the study treated with antidepressants, most were female, aged 50 years or older, non-Hispanic White, and who had a college education (HR 70.7%, 62%, 81.7%, and 69.4%, respectively).

More than two-thirds (67.9%) of the participants with MDD used selective serotonin reuptake inhibitors (SSRIs). Most had been on the same antidepressant medication for a "long time," the authors reported, with 79.2% and 67.8% taking them for more than 1 year and more than 2 years, respectively.

Despite the large number of patients on antidepressants, only 43% scored in the no/minimal symptoms range, according to the PHQ-9, whereas 28.4% scored in the moderate/severe range.

Most patients (85%) took 1 or more medications for medical conditions, with the majority taking medications with PDSS.

Number of Medications With PDSS

Percentage of Patients Using Them

≥ 1


≥ 2


≥ 3


≥ 4


≥ 5


Almost 75% were using 1 or more medications without PDSS, and 52% were using more than 1.

The number of medications with PDSS was significantly associated with lower odds for no/minimal depressive symptoms (adjusted odds ratio [aOR] 0.75 [95% CI: 0.64, 0.87]; P < .001) and higher odds for moderate/severe symptoms (aOR 1.14 [95% CI: 1, 1.29]; P = .044).

"The predicted probability of no/minimal symptoms in those taking 5 medications with PDSS was less than half the predicted probability in those taking no medications with PDSS (0.23 vs 0.52)," the authors reported.

Conversely, the predicted probability of moderate/severe symptoms was about 50% higher in individuals taking 5 vs 0 medications with PDSS (0.36 vs 0.24).

The researchers found no corresponding associations for medications without PDSS.

The results were even stronger when the researchers repeated their adjusted regression analyses to focus on the 10 individual medications most associated with the severity of depressive symptoms. These were omeprazole, gabapentin, meloxicam, tramadol, ranitidine, baclofen, oxycodone, tizanidine, propranolol, and morphine, with an aOR of 0.42 (95% CI: 0.3, 0.6) for no/minimal symptoms and 1.68 (1.24, 2.27) for moderate/severe symptoms.

"Many widely prescribed medications, from antihypertensives, such as atenolol and metoprolol to corticosteroids, such as dexamethasone and triamcinolone, are associated with depression side effects," said Olfson.

"These medications could interfere with recovery from depression. When available, consideration should be given to selecting a substitute with lower risk for depressive symptoms," he said.

Role in Treatment-Resistant Depression

Commenting for Medscape Medical News, Dima Qato, PharmD, MPH, PhD, Hygeia Centennial chair and associate professor, University of Southern California (USC) School of Pharmacy, said the study "is an important reminder that the use of medications with depressive symptoms side effects is increasingly common and may contribute to delays in responsiveness or worsen depressive symptoms among individuals being treated for depression."

Qato, who is also the director of the Program on Medicines and Public Health, USC School of Pharmacy, and was not involved with the study, recommended that clinicians "consider the role of medications with depression side effects when evaluating patients with treatment-resistant depression."

The study was not supported by any funding agency. Olfson and coauthors have disclosed no relevant financial relationships. Qato is a consultant for the Public Citizen Health Research Group.

Study Highlights

  • Investigators drew study data from 3 cycles of the NHANES from 2013 to 2018.
  • The current study was limited to survey participants who reported treatment with an antidepressant for ≥ 6 months to treat MDD. All persons contributing data to the current study were aged ≥ 18 years old.
  • Researchers assessed current symptoms of depression with the PHQ-9.
  • Participants provided health and demographic information as part of the survey. The main study analysis was how the use of medications with PDSS affected participants’ depression scores.
  • The following medications were considered to have PDSS:
    • Omeprazole
    • Meloxicam
    • Hydrocodone
    • Morphine
    • Ranitidine
    • Gabapentin
    • Tramadol
    • Baclofen
    • Tizanidine
    • Propranolol
  • The study results were adjusted to account for chronic health conditions as well as other medication use.
  • 885 adults contributed study data. 70.7% were female, and 62% were aged ≥ 50 years old. 81.7% were White, and 69.4% had a college education.
  • 67.9% of participants were treated with SSRIs. 79.2% of participants had been on their antidepressant for > 1 year.
  • 43% had no or minimal symptoms on the PHQ-9, but 28.4% had moderate or severe symptoms.
  • 85% used another prescription medication beyond their antidepressant, and 66.7% used a medication with PDSS. 21.6% of participants used ≥ 3 medications with PDSS.
  • Variables associated with a higher rate of symptoms of depression included Hispanic and Black race/ethnicity, lower educational attainment, and lower household income.
  • Chronic disease states associated with a higher rate of depression symptoms included arthritis, stroke, liver disease, and lung disease.
  • The aOR for having no or minimal symptoms among participants taking medications with PDSS vs no such medications was 0.75 (95% CI: 0.67, 0.85). The respective aOR for having moderate or severe symptoms was 1.22 (95% CI: 1.08, 1.27). Medications not suspected for PDSS did not significantly affect the symptoms of depression.
  • The probability of having no or minimal symptoms of depression was cut about in half as the number of drugs with PDSS increased from 1 to 5.
  • Individual medications substantially associated with significant increases in depression symptoms included omeprazole, gabapentin, meloxicam, morphine, tramadol, ranitidine, baclofen, oxycodone, tizanidine, and propranolol. Limiting the study’s main analysis to these 10 medications with PDSS yielded a stronger relationship between drug and severity of depression.

Implications for the Healthcare Team

  • A previous study by Rizvi and associates found that sleep disorders and chronic pain were particularly associated with higher rates of TRD. Type 2 diabetes, cardiovascular disease, chronic obstructive pulmonary disease, and hepatitis also were associated with higher rates of TRD, but arthritis, asthma, cancer, chronic kidney disease, peripheral vascular disease, and osteoporosis were not.
  • The current study by Mojtabai finds that the concomitant use of drugs with PDSS with antidepressants used to treat depression results in worse symptom scores for depression, with progressively worse results with more drugs with PDSS added.
  • The healthcare team should scan the medication list of adults with depression for medications with PDSS and then replace these drugs, if possible.


Earn Credit

  • Print