Effect of Zinc Supplementation on Depression in SSRI-treated Major Depressive Disorder Patients
Condition: MDD
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Study type: Interventional

Summary: 
      Title:

      Effect of zinc supplementation on depression in SSRIs-treated MDD patients.

      Purpose: Depression is the single largest contributor to global disability as has been ranked
      by WHO (2015), in humans including both male and female.Studies have suggested that
      conventional presently available anti-depressive medicines are effective for one third to
      one-half (19-34%) of the patients suffering from depression, leaving the rest of patients to
      suffer from recurrence or incomplete cure. Researchers throughout the world are involved to
      obtain new pharmacotherapy for the treatment of MDD. Zinc is an important micronutrient of
      the human body which is implicated as an essential component in various systemic wellbeing
      including the central nervous system.

      Methods: The study would be randomized, double-blind, placebo-controlled prospective
      interventional trial and it would be conducted in the Department of Pharmacology and in
      collaboration with the Department of Psychiatry, BSMMU, from date of approval by the IRB to
      August 2020. A total of 100 patients suffering from mild to moderate major depression will be
      selected following to inclusion and exclusion criteria and serum Zinc levels will be
      assessed. The diagnosis of patients suffering from MDD and the selection of drugs and dosage
      would be performed by a senior professor of the Psychiatry department. After completing the
      necessary formalities including the informed consent of the patients, the patient would
      undergo a selected questionnaire (DASS-21) to assess his/her degree of severity of the
      disease. The patients would be randomly allocated into two groups: group A (control group)
      and B (intervention group). Group A would consist of 50 patients who will receive a placebo
      with SSRIs for 8 weeks. Group B would consist of 50 patients who will receive SSRIs plus Zinc
      sulfate (30mg/day) orally for 8 weeks, after which at follow up, the severity of depression
      will be assessed. The blood sample will be collected to measure serum zinc level at baseline
      and again after 8 weeks of therapeutic intervention.

      Ethical consideration

      The study will follow the principles of the Declaration of Helsinki and of the World Medical
      Assembly. Patients will be informed about the study in easy language and then informed
      consent will be taken. The study has no potential risk to the patients. Confidentiality will
      be strictly maintained.
    

Detailed description: 
      Depression (MDD) is a major global health problem. The number of people suffering from major
      depressive disorder was reported as around 300 million (about 4.4% of the world's population)
      in 2015. The total number is assumed to increase to 18.4% from 2005 to 2015. Depression is
      more common in females compared to males (female: male = 5.1:3.6). Years lived with a
      disability are about 50 million people due to major depressive disorder and this disease has
      been claimed to be a major cause of morbidity, mortality, and also suicidal death. In
      Bangladesh, the prevalence of depressive disorder is about 4.1% and the percentage of total
      years lived with a disability (DALY) is about 7.1%. Within this number, some people suffer
      additionally from anxiety disorders and some suffer from both anxiety disorder and MDD.
      However, MDD has been assumed to occupy the place of the second cause of disability by 2020,
      and MDD, therefore, demands attention and alerts in clinical psychiatry. Depression impairs
      quality of life at the level of personal, familial, and social aspects and in the severe
      form, may lead to thoughts of committing suicide. Suicidal death (about 8,00000 per year)
      have been reported throughout the world in recent reports and are increasing gradually.
      Conventional antidepressants are the medicines used to treat MDD. Increasing 5HT
      concentrations at the synapses of the amygdala, frontal cortex, or the limbic region by SSRI
      or TCA or other drugs administration remains the primary object of therapy. About 19-34% of
      MDD patients show a reasonable level of response to the SSRIs while about 15-50% of patients
      show dissatisfactory response or recurrence. This fact is a subject of concern and invite
      pharmacological intervention either in the form of adjunct drugs or new drug discoveries.
      Recent researches have revealed that a significant role of zinc in MDD patients due to its
      antidepressant effects. Some studies reported that there is no effect of zinc supplementation
      on depression in MDD patients. Because of the conflicted reports, this study has been
      designed to evaluate the effect of zinc supplementation on depression in MDD patients treated
      with SSRI. Results of this study may be helpful to advocate the regular use of zinc
      supplementation as an adjunct to SSRI therapy in MDD. The study would be randomized,
      double-blind, placebo-controlled prospective interventional trial and it would be conducted
      in the Department of Pharmacology and in collaboration with the Department of Psychiatry,
      BSMMU, from the date of approval by the IRB to August 2020. A total of 100 patients suffering
      from mild to moderate major depression will be selected following to inclusion and exclusion
      criteria and serum Zinc levels will be assessed. The diagnosis of patients suffering from MDD
      and the selection of drugs and dosage would be performed by a senior professor of the
      Psychiatry department. After completing the necessary formalities including the informed
      consent of the patients, the patient would undergo a selected questionnaire (DASS-21) to
      assess his/her degree of severity of the disease. The patients would be randomly allocated
      into two groups: group A (control group) and B (intervention group). Group A would consist of
      50 patients who will receive a placebo with SSRIs for 8 weeks. Group B would consist of 50
      patients who will receive SSRIs plus Zinc sulfate (30mg/day) orally for 8 weeks, after which
      at follow up, the severity of depression will be assessed. The blood sample will be collected
      to measure serum zinc level at baseline and again after 8 weeks of therapeutic intervention.
      The regularity of medicine intake will be ensured over the telephone, counting the tablets,
      and from the patient's compliance sheet. The study entails almost no potential risk to the
      patients which will be explained to the patients together with the fact that he/she would be
      free to leave the study at any time and that he/she would receive free of cost treatment in
      case of any adverse reactions. Statistical analysis will be obtained by SPSS (Statistical
      Package for Social Science). Results will be presented in tables and graphical figures as
      applicable. Calculated 'p' value may suggest the level of significance (significant at p ≤
      0.050). The study will follow the principles of the Declaration of Helsinki and of the World
      Medical Assembly. Patients will be informed about the study in easy language and then
      informed consent will be taken. The study has no potential risk to the patients.
      Confidentiality will be strictly maintained.
    

Intervention name(s): SSRI with Zinc Sulfate
Intervention type(s): Drug
Intervention description(s): Zinc sulfate (30 mg) once daily for 8 weeks SSRI
Intervention MeSH terms: Zinc Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Zinc; SSRI; MDD