Pharmacist Disease State Guides
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      Diabetes and Depression

      Disease State Overview

      Patients with diabetes are more likely to have depression than people without diabetes. Depression is a condition characterized by low mood, a lack of positive thoughts, and a loss of interest in previously pleasurable activities that lasts longer than two weeks.  Depression may make it difficult for people to manage their diabetes causing an increased risk of diabetes associated complications like heart disease, stroke, and neuropathy. 
        

      Risk of Condition and Helpful Hints

      If either diabetes or depression are not managed effectively, it can lead to future complications.  
       

      Diabetes can lead to several microvascular and macrovascular complications.   

      1. Macrovascular complications of diabetes include coronary artery disease, peripheral arterial disease and stroke.   
      2. Microvascular complications of diabetes include diabetic nephropathy, neuropathy, and retinopathy.  

      Depression, if left untreated, may cause serious long-lasting symptoms and often disrupts a person’s ability to perform routine tasks. Untreated depression can increase a patient’s risk of developing other chronic health conditions and can also increase risk of death by suicide.  
       

      Adherence  

      Medication adherence is an essential component of treating diabetes and depression preventing further complications. Patients with both diabetes and depression are at a higher risk of being less adherent to medication regimens. Therefore, it is essential to discuss barriers to adherence and provide appropriate solutions with the patient. You may use the DRAW tool within the Worksheets & Forms category in this Knowledge Base.

      Adherence is also essential in the treatment of depression, as full response to pharmacotherapy typically occurs within the first 4–8 weeks of initial treatment. Educate the patient about the risks associated with sudden discontinuation of antidepressants. Symptoms may include changes in mood, irritability, anxiety, insomnia, headache, GI upset, or electric shock sensation. 

       

      Lifestyle Education  
      Managing diabetes can require a complex routine of medications, blood glucose, diet, physical activity and attending numerous medical appointments that can leave a patient feeling overwhelmed. This feeling is often referred to as diabetes distress and may cause patients to become frustrated and fall into unhealthy habits that may cause worsening of the disease.  

      Points to discuss with the patients may include the following:  

      • Make sure patients are seeing an endocrinologist for diabetes care.   
      • Encourage patients to discuss referral to a mental health counselor and/or a diabetes educator with their doctor.  
      • Encourage patients to focus on a couple diabetes management goals at a time.  
      • Help patients understand the benefit of joining a diabetes support group in their community or online.  

      Medication  

      Role of Medication – Diabetes  
      Type 1 Diabetes: Insulin therapy is required due to the body’s loss or near loss of beta cell function resulting in no or minimal endogenous insulin production. 

      Types 2 Diabetes: Guidelines recommended metformin and lifestyle modifications as initial therapy in patients with type 2 diabetes. Non-insulin medications can be used to increase the body’s sensitivity to insulin or stimulate production of endogenous insulin. As type 2 diabetes progresses, insulin supplementation may be required to achieve adequate blood glucose control. Choice of therapy should be based on multiple factors including A1c, medication side effect profile, insurance coverage, patient preference, patient’s age, comorbid conditions, and concurrent medications.  

      Medications for the Management of Diabetes from the American Diabetes Association (ADA)

      • Drug Class: Biguanide 
        • Drug Names:
          • metformin
        • Common Class Side Effects:
          • GI: diarrhea, nausea, vomiting, abdominal pain, bloating 
          • Weight change: neutral  
          • Hypoglycemia risk: No 
            • Taking with food may minimize GI upset 
      • Drug Class: Sulfonylurea 
        • Drug Names:
          • glipizide  
          • glimepiride 
          • glyburide  
        • Common Class Side Effects:
          • Weight change: gain  
          • Hypoglycemia risk: yes (glyburide > glimepiride > glipizide) 
      • Drug Class: Meglitinide  
        • Drug Names: 
          • repaglinide  
          • nateglinide  
        • Common Class Side Effects:
          • Weight change: gain   
          • Hypoglycemia: yes   
      • Drug Class: Thiazolidinedione
        • Drug Names: 
          • pioglitazone
        • Common Class Side Effects:
          • Weight change: gain 
          • Hypoglycemia risk: no 
          • Other: edema, bone fractures, congestive heart failure (BBW), increased LDL (rosiglitazone only), bladder cancer (pioglitazone only) 
      • Drug Class: DPP-4 Inhibitor 
        • Drug Names:
          • sitagliptin (Januvia) 
          • saxaglipitin (Onglyza) 
          • linagliptin (Tradjenta) 
        • Common Class Side Effects:
          • Weight change: neutral  
          • Hypoglycemia risk: no  
          • Other: nasopharyngitis, upper respiratory tract infections, headache, pancreatitis, joint pain 
      • Drug Class: GLP-1 Analog 
        • Drug Names:
          • exenatide (Byetta, Bydureon) 
          • liraglutide (Victoza)* 
          • dulaglutide (Trulicity)* 
          • semaglutide (Ozempic*, Rybelsus) 
        • Common Class Side Effects:
          • GI*: nausea, vomiting, diarrhea 
          • Weight change: loss  
          • Hypoglycemia risk: no 
          • Other: thyroid C-cell tumors (BBW), injection site reactions  
          • *GI side effects are minimized by starting the patient on the right starting dose and following the appropriate titration schedule  
      • Drug Class: SGLT2 Inhibitor 
        • Drug Names:  
          • canagliflozin (Invokana)* 
          • dapagliflozin (Farxiga) 
          • empagliflozin (Jardiance)*  
          • ertugliflozin (Steglatro) 
        • Common Class Side Effects:
          • Weight change: loss  
          • Hypoglycemia risk: no 
          • Other: Urinary tract infections, dizziness, hypotension, hyperkalemia 
      • Drug Class: Alpha Glucosidase Inhibitor 
        • Drug Names: 
          • acarbose 
          • miglitol 
        • Common Class Side Effects:
          • GI: diarrhea, flatulence 
          • Weight change: loss 
          • Hypoglycemia risk: no 
      • Drug Class: Amylin Analog 
        • Drug Names:
          • pramlintide
        • Common Class Side Effects: 
          • GI: nausea, vomiting 
          • Weight change: loss 
          • Hypoglycemia risk: no
      • Drug Class: Insulin
        • Drug Names:
          • Rapid Acting: 
            • aspart 
            • glulisine  
            • lispro  
          • Intermediate Acting:
            • NPH
          • Short Acting:
            • regular
          • Long Acting:
            • degludec  
            • detemir  
            • glargine 
        • Common Class Side Effects:
          • Weight change: gain  
          • Hypoglycemia risk: yes (highest risk)  

      * Demonstrated cardiovascular benefit in clinical trials and have a labeled indication of reducing CVD events. Consider in patients at high cardiovascular risk or in patients with established ASCVD.  

      Abbreviations used: DPP-4 = dipeptidyl peptidase-4, GLP-1 = glucagon-like peptide-1, SGLT2 = sodium-glucose cotransporter-2  

      Cardiovascular Disease Management in Diabetes  

      Cardiovascular disease (CVD) is the leading cause of death amongst people with diabetes making cardiovascular risk management an essential component diabetes management.  

      • Hypertension Therapy
        • Recommended Medication Options:
          • ACEi (first-line therapy), stands for angiotensin converting enzyme inhibitor
          • ARB (first-line therapy) , stands for angiotensin receptor blocker  
          • Calcium channel blocker 
          • Thiazide diuretic 
        • Rationale:
          • Hypertension is common in people with diabetes and increases risk of microvascular complications 
      • Lipid Therapy 
        • Recommended Medication Options:
          • Primary Prevention  
          • Moderate-intensity statin (all patients age 40 – 75 years)  
          • High-intensity statin (multiple ASCVD risk factors or age 40-75 years) 
          • Ezetimibe (consider adding to max tolerated statin in patients with ASCVD risk > 20%) 
          • Secondary Prevention  - High-intensity statin 
        • Rationale:
          • Statin therapy has been shown to decrease cardiovascular risk in people with diabetes with and without coronary heart disease.  
      • Antiplatelet Therapy 
        • Recommended Medication Options:
          • Primary Prevention  
          • Aspirin (high risk patients only)   
          • Secondary Prevention  
          • Aspirin 
          • Clopidogrel (patient with allergy to aspirin)  
          • DAPT (only used in certain patients) 
        • Rationale:
          • Aspirin has been shown to reduce cardiovascular morbidity and mortality in high-risk patients using for secondary prevention. For use in primary prevention, risk of bleed may outweigh potential benefit so risks should be discussed with the patient.  

      Administration  
      Pharmacists play a key role in the training and education of appropriate administration and storage of insulin and other injectables. Refer to the package insert or manufacturer website of the specific product for further guidance.   

       

       Role of Medication – Depression  
      The American College of Physicians recommends patient start on either pharmacologic therapy or cognitive behavioral therapy. Choice of therapy should be based on multiple factors including depression severity, depression features, medication side effect profile, medication tolerability, history of prior medication treatment, insurance coverage, patient preference, patient’s age, comorbid conditions, and concurrent medications.   
       

      Pharmacologic and non-pharmacologic treatment options as recommended by the American Psychiatric Association (APA) are outlined below. Medications should be titrated to maximally tolerated dose prior to switching or augmenting therapy.  

      Pharmacologic Management of Major Depressive Disorder  - Pharmacological Therapy

      • Drug Class: Selective serotonin reuptake inhibitor (SSRI)  
        • Medications:
          • citalopram  
          • escitalopram  
          • fluoxetine  
          • paroxetine  
          • sertraline   
          • fluvoxamine (FDA indicated for OCD only)
        • Class Side Effects:
          • CNS: insomnia, headache  
          • GI: nausea/vomiting, weight gain, dry mouth  
          • Other: hyponatremia/SIADH, sexual dysfunction, bleeding risk, QT prolongation* (*increased risk with citalopram doses > 40mg )
      • Drug Class: Selective serotonin-norepinephrine reuptake inhibitor (SNRI)  
        • Medications:
          • desvenlafaxine  
          • duloxetine  
          • levomilnacipran (Fetzima) 
          • milnacipran  
          • venlafaxine 
        • Class Side Effects
          • CNS: insomnia, headache  
          • GI: nausea/vomiting, weight gain, dry mouth  
          • Cardiac: hypertension, tachycardia/palpitations  
          • Other: hyponatremia/SIADH, sexual dysfunction   
      • Drug Class: Alpha-2 antagonist   

        • Other Classifications:   

          • Tetracyclic (TeTCA)    
          • Norepinephrine-serotonin modulator  
          • Noradrenergic and specific serotonergic (NaSSAs)  
        • Medications:
          • mirtazapine
        • Class Side Effects:
          • CNS: sedation  
          • GI: nausea, vomiting, constipation, weight gain  
          • Cardiac: increased cholesterol   
          • Other: dry mouth   
      • Drug Class: Dopamine norepinephrine reuptake inhibitor (DNRIs)  
        • Medications:
          • bupropion  
        • Class Side Effects:
          • CNS: insomnia, activation/anxiety, headache  
          • GI: nausea, weight loss, dry mouth  
          • Cardiac: hypertension, tachyarrhythmia,  
          • Other: seizures, diaphoresis  
      • Drug Class: Tricyclic antidepressants (TCAs)   
        • Medications:
          • Secondary Amine   
            • amoxapine  
            • desipramine  
            • nortriptyline  
            • protriptyline   
          • Tertiary Amine   
            • amitriptyline  
            • clomipramine (FDA indicated for OCD only)
            • doxepin  
            • imipramine  
            • trimipramine 
        • Class Side Effects:
          • CNS: sedation (less with secondary amine vs. tertiary amine TCAs)
          • GI: weight gain  
          • Anticholinergic: dry mouth, urinary retention, dry mouth, constipation, cognitive impairment  
          • Cardiac: QTc prolongation, arrhythmias, orthostatic hypotension (less with secondary amine vs. tertiary amine TCAs)
          • Other: sexual dysfunction, seizures   
      • Drug Class: Tetracyclic antidepressant (TeTCAs)  
        • Medications:
          • maprotiline
        • Class Side Effects:
          • CNS: sedation  
          • GI: weight gain  
          • Anticholinergic: dry mouth, urinary retention, dry mouth, constipation, cognitive impairment  
          • Other: blurred vision/visual disturbance    
      • Drug Class: Serotonin Modulators  (Selective Serotonin Reuptake Inhibitor/5-HT1A Receptor Partial Agonist) 
        • Medications:
          • vilazodone
        • Class Side Effects:
          • CNS: insomnia  
          • GI: nausea, vomiting, diarrhea   
          • Other: sexual dysfunction (potentially less than other agents)  
      • Drug Class: Serotonin Modulators  (Selective Serotonin Reuptake Inhibitor/Serotonin 5-HT1A Receptor Agonist/Serotonin 5-HT3 Receptor Antagonist)
        • Medications:
          • vortioxetine
        • Class Side Effects:
          • CNS: insomnia  
          • GI: nausea, vomiting diarrhea  
          • Other: sexual dysfunction (potentially less than other agents)
      • Drug Class: Serotonin Modulators (Serotonin Reuptake Inhibitor/Antagonist)
        • Medications:
          • trazodone  
          • nefazodone 
        • Class Side Effects:
          • CNS: sedation  
          • GI: nausea   
          • Cardiac: orthostatic hypotension  
          • Other: priapism (rare but serious; trazodone only)  
      • Drug Class: Monoamine oxidase inhibitor (MAOIs) 
        • Medications:
          • isocarboxazide  
          • phenelzine  
          • selegiline  
          • traylcypromine  
        • Class Side Effects:
          • CNS: insomnia, hypersomnia  
          • GI: weight gain  
          • Anticholinergic: dry mouth  
          • Cardiac: orthostatic hypotension, decreased heart rate,   
            peripheral edema, hypertensive crisis  
          • Other: sexual dysfunction
            • Note: MAOIs generally restricted to patients who do not respond to other therapies

       Non-Pharmacological Therapy

      • Psychotherapy
        • Transcranial magnetic stimulation (TMS)
      • Electroconvulsive therapy (ECT)  
        • Light therapy

        

      Administration  
      Most antidepressants may be taken at any time of day. If the medication makes the patient feel stimulated or drowsy, they may need to change the time of day they take the medication.   
        

      Monitoring

      Diabetes  
      The goal of therapy is to reduce microvascular and macrovascular complications by achieving and maintaining glycemic control while minimizing the risk of side effects. Treatment should be reassessed and modified on a regular basis (every 3-6 months) to ensure treatment appropriateness and efficacy.   
        
      Hemoglobin A1c  
      A1c should be monitored every 3 months if uncontrolled and every 6 months if controlled. Although target A1c should be individualized per patient, the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologist provide the following recommendations:   

      • ADA
        • General Recommendations: <7
        • Older Adults: <7 - 7.5
      • ACCE
        • General Recommendations: <6.5

        

      Blood glucose  
      Blood glucose should be monitored regularly in patients with diabetes and can be self-monitored in many cases. Glucose targets may be altered based on many factors including duration of diabetes, age/life expectancy, and comorbid conditions. However, general recommendations are outlined below:   

      • ADA
        • Fasting/Pre-prandial: 80-130 mg/dL
        • Peak post prandial: < 180 mg/dL
      • ACCE
        • Fasting/Pre-prandial: <110 mg/dL
        • Peak post prandial: <140 mg/dL

        

      Health Screenings  
      In addition to regular monitoring of A1c and blood glucose, patients with diabetes should receive the following screenings/exams:  

      • Eye exams (at least annually)   
      • Renal function (at least annually)   
      • Blood pressure screenings (at every routine visit)   
      • Foot exams (at least annually)   
      • Dental exams  

        

      Depression  
      Frequent follow-up should be scheduled with the patient’s prescriber to monitor response to treatment, adherence to the treatment plan, and suicide risk. Close observation and communication with the prescriber should be recommended to both the patient and their family.   

      The Patient Health Questionnaire (PHQ-9) is a common tool used to monitor both the severity of depression and response to treatment. Monitoring should also include screening for other mental disorders or chronic conditions.   

        

      Additional Points

      Diabetes  
      Immunization Assessment:  
      It is important to review a patient’s immunization history and recommend vaccines that are important in patients with diabetes by the Advisory Committee on Immunization Practices (ACIP) and the Centers for Disease Control and Prevention (e.g. influenza, pneumonia, Hepatitis B).  

       

      Hypoglycemia Education:  
      Patients should be instructed how to treat and monitor for signs and symptoms of hypoglycemia, including: dizziness, hunger, sweating, shakiness, confusion, and lightheadedness. Hypoglycemia in patients with diabetes is generally defined as a blood glucose of < 70mg/dL.   
        

      Rule of 15 for Treating Hypoglycemia 

       

      Depression  
      Patients with depression should be counseled on the following points related to pharmacologic treatment:  

      • All antidepressants carry a black box warning of increased risk of suicidality in children, adolescents, and young adults ≤ 24 years of age. Advise patients who have thoughts about hurting themselves to go to the emergency room, contact their provider or call the National Suicide Prevention Hotline at 988 or visit www.suicidepreventionlifeline.org.  
      • Some medication side effects may resolve within the first few weeks of treatment initiation, so it is important to continue therapy if side effects are tolerable.   
      • The signs and symptoms of serotonin syndrome include mental status change, autonomic hyperactivity, and neuromuscular abnormalities. Patients should seek immediate medical attention should they occur.  



       Resources:  

      1. American Diabetes Association. Standards of Medical Care in Diabetes – 2024. Diabetes Care 2024.   
        https://diabetesjournals.org/care/issue/47/Supplement_1 
      2. American Psychological Association (APA). Practice Guideline for the Treatment of Patients with Major Depressive Disorder (3rd edition). American Psychiatric Association.  
        https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf 
      3. American Psychological Association (APA). Treating Major Depressive Disorder: A Quick Reference Guide.  
        https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd-guide.pdf 
      4. Blonde L, Umpierrez GE, Reddy SS, et al. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update [published correction appears in Endocr Pract. 2023 Jan;29(1):80-81. doi: 10.1016/j.eprac.2022.12.005]. Endocr Pract. 2022;28(10):923-1049. doi:10.1016/j.eprac.2022.08.002 
        https://pubmed.ncbi.nlm.nih.gov/35963508/ 
      5. Centers for Disease Control and Prevention (CDC). Diabetes and Mental Health.  
        https://www.cdc.gov/diabetes/living-with/mental-health.html?CDC_AAref_Val=https://www.cdc.gov/diabetes/managing/mental-health.html 
      6. Chapman DP, Perry GS, Strine TW. The vital link between chronic disease and depressive disorders. Prev Chronic Dis [serial online] 2005;2(1).   
        https://pubmed.ncbi.nlm.nih.gov/15670467/  
      7. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive Type 2 Diabetes Management Algorithm – 2020 Executive Summary. Endocr Pract. 2020;26(1): 107 – 139. 
        https://www.endocrinepractice.org/action/showPdf?pii=S1530-891X%2820%2935066-7  
      8. Qaseem A et al. Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients with Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians. Annals of Internal Medicine.  
        https://www.acpjournals.org/doi/10.7326/M15-2570