Treatment for Depression

Treatment for Depression Frederick Troncales, MD PGY 1 – internal medicine Brown University/MHRI What are the Stats related to Depression?  Lifetime risk of Major Depression is 712% in men and 20-25% in women  6.7 percent of the population, or about 14.8 million American adults, will struggle with depressive illness  80% of depressed people are not currently having any treatment More Depression Stats  15% of depressed people will commit suicide  Depression will be the second largest killer in 2020 after heart disease- and it has been shown to be contributory to fatal heart disease ( WHO 2001)  Depression results in more absenteeism than almost any other physical d/o costing $51 Billion per year in lost productivity What is the pathophysiology of Depression?  It has not clearly been defined  Clinical and preclinical trials suggest disturbance in CNS serotonin activity.  Other neurotransmitters implicated include NE and dopamine  Clinical experience indicates a complex interaction between NT availability, receptor regulation and sensitivity and symptoms of MDD How do I diagnose Depression? DSM IV  *Depressed mood most of the day, particularly in the morning  *Markedly diminished interest or pleasure in almost all activities nearly every day (anhedonia); these can be indicated by the subjective account or observations by significant others  Significant weight loss or gain  Insomnia or hypersomnia  Psychomotor agitation or retardation  Fatigue or loss of energy  Feelings of worthlessness or guilt  Impaired concentration, indecisiveness  Recurring thoughts of death or suicide  Symptoms should be present daily or for most of the day, or nearly daily for at least two weeks.  Must cause clinically significant distress or impairment in functioning  Not due to the direct effects of a substance (eg, drug abuse or medications) or a medical condition (eg, hypothyroidism)  Do not occur within two months after the loss of a loved one  A history of a prior manic episode in addition to these criteria suggests the diagnosis of bipolar disorder. How do I evaluate somebody with depression?  Patients should have History, PE, and limited laboratory testing completed to rule out secondary medical causes  Should be screened for Bipolar Disorder  Assess for the presence of suicidal / homicidal ideation  Assess if they have access to means of suicide  Presence of Psychotic symptoms, command hallucinations, severe anxiety  Presence of alcohol and substance abuse PHQ - 9  Allows measurement of diagnosis and severity of major depression  Can monitor response to treatment  To guide titration of antidepressant medication or response to psychotherapy What can I say to somebody who’s depressed?  Many patients are reluctant to accept a diagnosis of depression  Maybe important to stress that Depression is common  Frequently assoc. with fatigue, headache, abdominal pain  It is a physical illness assoc with biologic changes in the brain including depletion of key chemicals called catecholamines  Treatment with either medication or psychotherapy generally shortens the course and diminishes symptoms such as fatigue, poor self esteem, etc.. How can I improve my patient’s compliance to Medications?  Patients should be told  Do not stop medications without talking to doctor  There is LAG of 2-3 weeks before medications will relieve most symptoms  S/E occur frequently during first few days but are gone after a week What are the different Antidepressants?  Major Classes      SSRI TCA Heterocyclics (Bupropion) MAO Inhibitor Meds that inhibit both NE and Serotonin reuptake – Venlafaxine and Duloxetine  All available antidepressants appear to work via 1 or more of the following mechanisms:  (1) presynaptic inhibition of uptake of 5-HT or NE;  (2) antagonist activity at presynaptic inhibitory 5-HT or NE receptor sites, thereby enhancing neurotransmitter release;  (3) inhibition of monoamine oxidase, thereby reducing neurotransmitter breakdown. How effective are antidepressants?  Studies concluded that antidepressants have a 50-60% response rate in the primary care setting Which antidepressant should I use?  Number of clinical studies and reviews have concluded that clinical outcomes, quality of life outcomes and overall treament costs provide no clear guidance on choice  Most compelling reason SSRI are used as 1rst choice in primary care is lower severity of S/E and less danger with overdose What are the Side Effects? How do I start antidepressants?  Starting at low doses can minimize the side effects of anitdepressants      Paroxetine 5-10 mg / day Sertraline 12.5 to 25 mg / day Fluvoxamine 25 mg /day Escitalopram 10 mg / day Citalopram 20 mg / day  Give for a week then gradually titrate up to full doses  Usually taken in the morning  For the first 8-12 hours can be stimulating and may disturb sleep How do I follow up?  Patients need to check in every 2 weeks for 68 weeks during initiation phase of medication treatment  Initial therapeutic response typically occurs w/in 2 – 6 weeks  More than half of eventual responders begin to respond by week 2  Little evidence to support extending antidepressant therapy beyond 6 weeks in patients who have shown no response to maximal therapy What do I do if patient does not respond?  If there is no response by 8 – 12 weeks at a maximum therapeutic dose…  Patient should be given a second trial of another antidepressant (same or different class)  Patient’s antidepressant meds can be augmented with second drug such as Bupropion or Buspirone  May refer to a psychiatrist What could possibly cause treatment resistance?  Only 50% of patients in primary care respond to first choice of antidepressant  20% stop medication due to S/E  30% have no response  Evaluate patient for chronic social stressors than can limit response to txt  Panic d/o, PTSD, Marital discord, childhood adversity, alcohol/substance abuse  Undiagnosed Bipolar d/o How long should I treat?  Antidepressant medication taken at least 6-9 months  Inform patient that medication leads to a genuine change in underlying neurochemistry  It takes weeks to adjust to being on/off  Should be tapered off to minimize s/e Are Antidepressants safe in Pregnancy?  As with other drug use during pregnancy, decision to treat depends upon balance of risks and benefits  Placebo controlled trial done on Fluoxetine, TCA showed no difference in risks of developing major fetal malformations, low IQ scores, behavioral devt  There maybe some adverse effect on fetus yet to allow a woman suffer from symptomatic depression during pregnancy can also result in unacceptable costs to mother and the fetus What do we do then?  Mild to moderate depressed pregnant patients  Should be treated with psychotherapy  Severely depressed pregnant patients or those unresponsive to psychotherapy should receive pharmacotherapy  SSRI’s are pregnancy category C Do patients relapse?  Relapse is relatively common once patients with major depression stop txt  2 major risk factors for relapse  Persistence of subthreshold depressive sx’s 7 months after initiation of antidepressant txt  History of 2 or more episodes of MD for 2 years What do we do with patients that relapse?  Maintainance antidepressant txt can decrease rate of relapse  AHPCR Guideline Panel recommended maintainance therapy for patients w/ a history of 3 or more depressive episodes and those with 2 depressive episodes plus risk factors that increase recurrence risk What is Electric Convulsive Therapy?  Highly effective in pt w/ psychotic depression  Effective for patient w/ severe melancholic depression on maximum medical therapy  Meta-analysis of randomized trials concluded that ECT is an effective therapy for depression and is probably more effective than pharmacotherapy  Decision for should be made with Psychiatrist  Role of Primary care provider is to address patient’s fears and emphasize that the often quick response and low side-effect profile make it one of the most effective txt “It seemed like this was one big Prozac nation, one big mess of malaise. Perhaps the next time half a million people gather for a protest march on the White House greens, it will not be for abortion rights or gay liberation…. but because we’re all so BUMMED out.” Elizabeth Wurtzel Author THANK YOU

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