Clinical Practice Guideline: Depression in 4 Taft Court Rockville, MD 20850 www.mamsi.com 40 05 17 035 3/03
Once a primary care patient presents with depressive symptoms, the primary care physician makes a clinical decision to refer to a psychiatrist, or to diagnose and begin treating the depression. The following items elaborate on the numbered cells on the Depression in Primary Care Medication Workflow. When the patient presents with depressive symptoms in primary care: 1. Symptoms are presented in primary care: a. Make the diagnosis Depression may present with: i. Pain ii. Low energy and reduced capacity for pleasure or enjoyment iii. Apathy, irritability, anxiety, prolonged sadness iv. Sexual complaints functioning and/or desire v. Concurrent general medical illnesses vi. Concurrent substance abuse vii. Symptoms of fatigue or malaise Additional risk factors for depression: viii. Recent stressful life events and lack of social supports (e.g. recent death, job loss or transition, major life event (positive or negative), divorce, domestic violence) ix. Prior episodes of depression x. Family history of major depressive or bipolar disorder b. Evaluate patients with complete medical history, psychosocial history, and physical examination c. Detect depressive symptoms with a clinical interview The following are the diagnostic criteria for major depressive disorder: i. Depressed mood most of the day, nearly every day ii. Markedly diminished interest or pleasure in almost all activities most of the day, nearly every day iii. Significant weight loss/gain iv. Insomnia/hypersomnia v. Fatigue vi. Psychomotor agitation/retardation vii. Feelings of worthlessness viii. Impaired concentration ix. Recurrent thoughts of death or suicide d. Identify and treat potential known causes (if present) of mood disorder Generally, the principle is to treat the associated condition first. If the depression persists after treatment of the associated condition, major depressive disorder should be diagnosed and treated. Potential associated conditions include: i. Substance abuse ii. Concurrent medication idiosyncratic side effect of medications Page 1 of 9
iii. iv. General medical disorders Eating disorders, anxiety disorders (when generalized anxiety disorder co-exists, treatment should target the major depressive disorder first) 2. Referral to a psychiatrist can be useful in the following situations: a. When primary care general guidelines may not be suitable for the patient b. The patient is actively suicidal c. The patient is experiencing a deterioration in mental status such that the ability to function is compromised d. The patient s symptoms suggest a complex psychiatric diagnosis e. Diagnostic uncertainty 3. Initiate medication treatment (see flowchart for specifics) Medications should be individualized to the patient in order to optimize treatment benefit and lower risk. Factors to be considered include: i. Possibility of short and long-term side effects ii. History of response or non-response to adequate trials of mediations iii. Consideration of possible drug interactions iv. Presence of other psychiatric and general medical conditions Should no response, or partial response occur during the first six weeks of therapy, re-evaluate the diagnosis, evaluate for side effects, and inquire about medication adherence. Determine the need for increasing the dosage. In addition, a change in medication may be required. Patients who do not respond to the initial medication trial are likely to respond to an alternate drug. Patients at risk of experiencing adverse drug interactions or with other medical illnesses may need lower-thanrecommended dosages. See Table 1 for a list of antidepressants with therapeutic ranges, side effects, and special considerations. 4. Evaluate the need for maintenance phase treatment Individual characteristics of the patient should be considered when evaluating the need for maintenance medication. Circumstances to consider include, but are not limited to, patients who have had two or more previous episodes of depression, and patients with a family history of depression. 5. Seek consultation Consultation with or referral to a psychiatrist can be useful in the following situations: a. The patient fails to respond fully to one or two medication trials b. The patient shows persistent psychosocial problems c. Formal psychotherapy is a consideration d. Diagnostic uncertainty 6. Patient education Continuing patient education and support significantly increases the likelihood of medication adherence. Patient education includes, but is not limited to: a. Encouraging patients to take medication as prescribed b. Advising that medication may need to be taken for two to four weeks for a noticeable effect Page 2 of 9
c. Counseling the patient to continue taking medication even if he or she begins to feel better d. Reminding the patient to not stop the medication without consulting the physician e. Asking the patient to contact the physician s office with questions about medication (dosing, possible side effects, issues concerning missed doses, alternative treatment) f. Advising that some side effects are common at the beginning of treatment these side effects may resolve themselves as the patient adjusts to the medication or not discontinuing their medication without prior consultation with the physician g. Warning that alcohol has the potential for diminishing the effects of antidepressants. Page 3 of 9
References 1. Depression Guideline Panel. Depression in Primary Care: Volume 1. Detection and Diagnosis. Clinical Practice Guideline, Number 5. Rockville, MD. U.S. Department of Health and Human Services, Public Health Service Agency for Healthcare Policy and Research. AHCPR Publication No. 93-0550. April 1993. 2. Depression Guideline Panel. Depression in Primary Care: Volume 2. Treatment of Major Depression. Clinical Practice Guideline, Number 5. Rockville, MD. U.S. Department of Health and Human Services, Public Health Service Agency for Healthcare Policy and Research. AHCPR Publication No. 93-0551. April 1993. 3. Physicians Desk Reference, 53rd Edition, 1999. Medical Economics Company, Inc.; Montvale, NJ. 4. Physicians Desk Reference, 55th Edition, 2001. Medical Economics Company, Inc.; Montvale, NJ. 5. Professional s Handbook of Psychotropic Drugs (2001). Springhouse Corporation; Springhouse, PA. 6. Escitalopram Oxalate. Prescribing Information (2002). Forest Pharmaceuticals, Inc. 7. Paroxetine Hydrochloride, Controlled-Release Tablets. Prescribing Information (2002). GlaxoSmithKline; Research Triangle, NC. 8. Paroxetine, Oral Suspension. Prescribing Information (2002). GlasoSmithKline; Research Triangle, NC. Page 4 of 9
Markedly Improved Continue treatment at least until week 12; end of acute phase Markedly Improved? Medication continued until week 24; end of continuous phase Consider maintenance treatment 4 Depression in Primary Care Medication Workflow (Adult) Patient Presents in Primary Care (Evaluate complete medical history and review most recent physical examination, or conduct physical examination) Make Diagnosis 1 Initiate Medication Tx 3 Monitor Acute Treatment (every 1-2 weeks) Assess Response (week 6) No Response Yes Diagnosis Correct? No Treat Primary Problem No Adjust Dose, Counsel Adherence Consultation Augment Referral 5 Medication Change Medication Refer to Specialist If not improved Markedly Improved Re-evaluate at 12 weeks Refer to Psychiatrist 2 Partial Response (Largely Cognitive Symptoms Remain) (Largely Vegetative Symptoms Remain) Change or Augment Medication Page 5 of 9
Table I: Dosage Requirements may be decreased in geriatric patients and daily doses may need to be adjusted. All SSRIs can have possible drug-drug interactions. Drug Name Adult Starting Dose (Range) mg/d Avg. Maint. Dose Common Side Effects Predominant Effects Special Considerations Citalopram* (Celexa) 20mg (20-60mg) 20-40mg tremor, nausea, dry mouth, sexual dysfunction, loose stools, anorexia Low Cyt p-450 enzyme effects. Escitalopram Oxalate* (Lexapro) 10mg (10-20mg) 10-20mg Insomnia, diarrhea, dry mouth, somnolence, dizziness, sweating, constipation, fatigue, and indigestion s FDA-approved for Major Depressive Disorder only Fluoxetine* (Prozac) 20mg (20-80mg) 20mg anxiety dizziness, sweating, nausea, diarrhea, dry mouth, headache, OCD, used for bulimia Long half-life Fluvoxamine* (Luvox) 50mg (100-300) not to exceed 300mg dizziness, nausea, diarrhea, headache, sexual dysfunction Antianxiety FDA-approved for OCD only Paroxetine HCL* Paroxetine CR* (Paxil) 20mg (20-50) 30mg 25mg (25-62.5) 30mg anxiety, tremor, seating, nausea, diarrhea, sexual dysfunction. Sedative properties used for OCD, panic disorder, and social phobia Withdrawal syndrome involves flu-like symptoms, sedative properties Paroxetine Oral Susp.* (Paxil Oral Suspension) 5mL (5mL-25mL) 15mL anxiety, tremor, seating, nausea, diarrhea, sexual dysfunction. Sedative properties used for OCD, panic disorder, and social phobia Withdrawal syndrome involves flu-like symptoms, sedative properties Sertraline* (Zoloft) 25mg (50-200) 70mg anxiety, dizziness, rash, nausea, diarrhea, sexual dysfunction, OCD, panic disorder, posttraumatic stress Withdrawal syndrome involves flu-like symptoms, low Cyt P-450 enzyme effects Page 6 of 9
Table I: Dosage Requirements may be decreased in geriatric patients and daily doses may need to be adjusted. All SSRIs can have possible drug-drug interactions. Others General comments: Use caution in advanced atrio-ventricular delay, potentially lethal in overdose, blood levels useful from some (i.e. desipramine and nortriptyline). Can cause dry mouth, constipation, blurred vision, urinary retention, postural hypotension, tachycardia, somnolence, weight gain. Drug Name Adult Starting Dose (Range) mg/d Avg. Maint. Dose Common Side Effects Predominant Effects Special Considerations Bupropion* (Wellbutrin) 200mg (150-450) lowest dosage that maintains remission Insomnia, headache, constipation, dry mouth, nausea, tremor, minimal sexual dysfunction Seizure rate = 4% if dose exceeds 450mg/day. Available in sustained release Bupropion SR* (Wellbutrin) 150mg (150-400) lowest dosage that maintains remission (See Above) Mirtazapine (Remeron) 15mg (15-45) Somnolence, dry mouth, constipation, increased appetite Given at bedtime to help sleep Nefazadone HCl (Serzone) 200mg (300-600) 438mg Nausea, dry mouth, dizziness, sedation, agitation, constipation Cases of life threatening hepatic failure have been reported. No sexual dysfunction. Trazadone (Desyrel) 150mg (150-600) mean dose to sustain remission Dizziness, drowsiness, headache, nervousness, dry mouth, headache Smaller dose for insomnia Venlafaxine* (Effexor) 75mg (75-375mg) mean dose to sustain remission Insomnia, nervousness, nausea, sweating, dizziness, headache, Antianxiety No Cyt P-450 drug interactions. Sustained release available Venlafaxine XR* (Effexor) 75mg or 37.5 (75-225) mean dose to sustain remission (See Above) Page 7 of 9
Tricyclics Secondary Amines Drug Name Adult Starting Dose (Range) mg/d Avg. Maint. Dose Common Side Effects Predominant Effects Special Considerations Amoxapine (Asendin) 50-100mg (100-600) Dizziness, drowsiness, tardive dyskinesia, NMS, seizures, orthostatic hypotension, tachycardia, blurred vision, constipation, dry mouth, acute renal failure, diaphoresis High risk of seizures, NMS, high fever, prolonged QT intervals, elevation of liver enzymes Desipramine (Norpramin) 100mg (100-300) vision, constipation One the least sedating and least anticholinergic of the tricyclics Nortriptyline (Pamelor, Aventyl) 75-100mg (75-150) vision, constipation One of the least likely to cause orthostatic hypotension of tricyclics Protriptyline (Vivactil) 15-40mg (15-60) vision, constipation Least sedating tricyclic. May cause insomnia Tetracyclics Maprotiline 75mg (75-225) Dizziness, drowsiness, EPS, seizures, arrhythmias, heart block, orthostatic hypotension, blurred vision, constipation, diaphoresis High risk of seizures. Hypomania is rare but can happen Page 8 of 9
Table II: Tricyclics Tertiary Amines Drug Name Adult Starting Dose (Range) mg/d Avg. Maint. Dose Common Side Effects Predominant Effects Special Considerations Amitriptyline (Elavil) 75mg (100-300) 50-100mg vision, constipation, arrythmias, orthostatic hypotension Used for insomnia and chronic pain syndrome Clomipramine (Anafranil) 25mg (100-250) vision, constipation, orthostatic hypotension, arrythmias, sexual dysfunction Antiobsessional Useful in depressed patient with strong obsessional features, higher risk of seizures Doxepin (Sinequan) 75mg (25-300) 150mg vision, constipation, orthostatic hypotension, sedation, Antianxiety Use for insomnia and chronic pain syndromes Imipramine (Trofranil) 25-50mg (25-300) vision, constipation Used for childhood enuresis, and chronic pain syndrome Trimipramine (Surmontil) 50-75mg (50-300) 50-150mg vision, constipation Most effective for endogenous depression Page 9 of 9