Depression Presenter: Robert R Edger MD  Goals:  How to identify it  How to assess suicide potential  What medications used to treat depression  Course of the illness  This talk should give some ideas about what questions you should ask your doctor about this illness.

What is Major Depression?  A complex interaction between multiple vulnerability genes and environmental factors  It is a chronic and recurrent illness and may be progressive, in that there may be structural changes in the brain at a cellular level e.g., changes in cortical thickness and neurodegeneration.  Associated with changes in endocrine function, immune function and autonomic function: e.g. obesity, hypertension, increase cholesterol, increased inflammation

Epidemiology  National Comorbidity Survey-Replication showed life time prevalence of 16.2%; 12 month prevalence 6.6%  Delay in treatment is on average 3 years  It is the leading cause of disability in the world according to WHO  Women: Men 2:1  Only about a quarter of people with it ever get treated

Neurobiology  Stress and trauma, early and late life adversity for example child abuse, can result in the way genes function in the brain  Neurocircuitry controlling mood is effected: disconnect between cortical regulation and deeper structures in the brain  This leads to emotional dysregulation, cognitive impairment, behavioral symptoms, physical impairment and systemic manifestations like tiredness

Psychiatric Management of Depression  One of the best predictors of success in treating depression is establishing a good relationship with your doctor. If possible get family to come with you to give history  Tell the doctor if there were past treatment response, hospitalizations, suicide attempts  Was there any past abuse, trauma, substance use, medical conditions, sexual dysfunction, problems at work, and in relationships; problems in the military

Assessment  Family History: of mental illness, legal problems, substance abuse, suicide  Medical Conditions that may present as depression: thyroid disease, stroke, Parkinson’s disease, dementia, metabolic conditions, e.g. hypercalcemia, diabetes; malignancy, infections.  Medications that induce depression: anti- rejection agents, chemotherapy agents, interferon, steroids, antibiotics, accutane

Assessment  Is there Psychosis, Bipolar mood swings, mixed mania, switch to mania secondary to antidepressants (20% risk)  Psychosis is where there are hallucinations, paranoia, judgment and insight are gone  Bipolar Disorder is characterized by mood swings: highs and lows  Screening tools: Patient Health Questionnaire-9 (PHQ-9)

Suicide Assessment  We may hide suicidal/homicidal ideation as it is such frightening territory  Try to get collateral information: family, friends; elicit their support in monitoring; assess whether there is intent, not just thoughts of suicide  Are there lethal means available: guns  Be aware of potential for aggression and homicide, especially in patients with history of violent behavior and in post partum depressions

Factors to Consider in Assessing Suicide Risk  Lifetime history, nature, seriousness, and number of previous attempts and aborted attempts  Presence of hopelessness, psychic pain, decreased self-esteem, narcissistic vulnerability. Presence of severe anxiety, panic attacks, agitation, impulsivity

Factors to Consider in Assessing Suicide Risk Nature of cognition, such as loss of executive function, thought constriction (tunnel vision), polarized thinking, closed-mindedness, poor coping and problem-solving skills  Presence of psychotic symptoms, such as command hallucinations or poor reality testing  Presence of alcohol or other substance  Recent psychiatric hospitalization

Older male adults highest risk; teens risk of copy cat suicide Presence of disabling medical illness Presence of acute or chronic psychosocial stressors, actual or perceived interpersonal losses, financial difficulties or changes in socioeconomic status (retirement), family discord, domestic partner violence Factors to Consider in Assessing Suicide Risk

Absence of psychosocial support, such as poor relationships with family, unemployment, living alone, unstable or poor therapeutic relationship, recent loss of a relationship History of childhood traumas, particularly sexual and physical abuse Family history of or recent exposure to suicide especially in teenagers, copy cat attempts Absence of protective factors, such as children in the home, sense of responsibility to family, pregnancy, life satisfaction, cultural beliefs, or religiosity Factors to Consider in Assessing Suicide Risk

Enhance treatment Adherence  Explain: when and how often to take medicine  Reminder systems: pill boxes, alarms  Take medications for several weeks to get benefit  Take medication even after feeling better  Consult with doctor before d/c of medication  Tell your doctor about concerns and fears, understanding of meds, correct misconceptions  Explain what to do if problems arise  Concerns about cost need to be discussed: use generics, patient assistance programs

Education of Patient and Family Depression is not a moral defect but a medical illness; the family may be convinced there is nothing wrong  Explain course of treatment: first side effects may occur, neurovegetative symptoms may remit, then mood improves  Identify stressors that may trigger relapse  Encourage routines: sleep/wake cycle, eating, exercise, decrease alcohol, caffeine, tobacco products

Pharmacotherapy The range of possible treatments: psychotherapy, medications, Light Therapy, ECT, complementary and alternative medications There are no replicable, robust findings to suggest one agent is superior to another No psychotherapy has been shown robustly to be better than others; psychodynamic, interpersonal therapies may have more benefit

Antidepressant Medications  They do differ in their potential to cause side effects; if they are going to work it will be in the first 1-2 weeks  SSRI’s, SNRI’s Mirtazapine and Bupropion are optimal agents to try first; Bupropion also has an indication for smoking cessation

Selective Serotonin Reuptake Inhibitors (SSRI)  Citalopram (Celexa)  Escitalopram (Lexapro)  Fluoxetine (Prozac)  Paroxetine (Paxil)  Sertraline (Zoloft)  Vilazodone (Viibryd)  Dose depends on the individual; elderly need lower doses; GI Side effects; sexual side effects most common; seizures; fall risk; Osteopenia; weight gain

NDRI Norepinephrine Dopamine Reuptake Inhibitors  Bupropion (Wellbutrin)  Beware in using it if you have a seizure history  Don’t use it with a history of bulimia  Commonly used with other antidepressants although no proof that it helps

Serotonin Norepinephrine Reuptake Inhibitors SNRI  Venlafaxine (Effexor)  Desvenlafaxine (Pristiq)  Duloxetine (Cymbalta)  Side effects may include elevated blood pressure, headaches, sexual dysfunction, sleep disruption

Other Antidepressants  Serotonin Modulators: Nefazodone, Trazodone  Nefazodone: can rarely cause liver damage  Norepinephrine Serotonin Modulator: Mirtazapine  Mirtazapine (Remeron) can stimulate appetite and be useful in cancer treatment; it can raise cholesterol and be sedating; can be a good add on medication; helps with sleep

Tricyclic Antidepressants  Amitriptyline, Doxepin, Imipramine, Desipramine, Nortriptyline  Many side effects: cognitive impairment, narrow angle glaucoma, delirium, fall risk, urinary retention, cardiac arrhythmia, orthostatic hypotension, constipation, dry mouth, seizures, sedation, sexual dysfunction, can be lethal in overdoses

Monoamine Oxidase Inhibitors (MAOI),Folic Acid, Omega3  Phenelzine, Tranylcypromine, Isocarboxazid  Selegeline (Emsam) Patch  Dietary restriction: no aged cheese or meats; red wine, draft beer, fava or broad beans  Risk of hypertension and stroke  L-Methylfolate (Deplin)  Omega 3 use between mg daily

Response to Treatment  Remission is the goal: at least 3 weeks without sad mood or reduced interests and no more than 3 symptoms of depression remaining.  This only occurs in about 40-45% of patients in the best of hands  Residual symptoms predict recurrence.  If you don’t respond in 2 weeks to a medication, consider adding medication, or augmentation

Augmentation  Lithium: most studied adjunct. Useful in suicide prevention. Blood level of Lithium to attain has not been confirmed. Use at night as there is less risk to renal side effects.  Thyroid supplementation: triiodothyronine mcg/day.

Augmentation: Atypical Antipsychotics  May increase the rate of response or remission to people who haven’t responded to 2 or more antidepressant trials, even if psychotic symptoms are not present  Use lower doses:  Olanzapine: (Zyprexa); Aripiprazole (Abilify); Quetiapine (Seroquel); metabolic side effects limit utility (weight gain, diabetes)

Augmentation  Stimulants: methylphenidate (Ritalin)or Dextroamphetamine (Adderall)  Modafinil (Provigil) and Nuvigil: may help with fatigue or hypersomnolence (caution when using with Oral Contraceptives)  Anticonvulsants: carbamazepine (Tegretol), valproic acid (Depakote), Lamotrigine (Lamictal).

Continuation Phase  Treat at least 4-9 months to prevent relapse assuming good control of depression  The risk of relapse is highest in the first 6 months after remission  Use same dosing as during the acute phase  Monitor for contributors to relapse: substance use, general medical conditions, psychosocial stressors, decrease adherence to medications

Maintenance Phase  Within the first 6 months following recovery from a major depression, 20% of patients will experience a recurrence.  Between 50-85% of patients will have a life time recurrence usually within 2-3 years  The risk of subsequent recurrences increases by 16% with each successive episode.  Patients with prior episodes of depression are at risk for mania, hypomania, dysthymia or chronic low grade depression

Maintenance Phase  People who have had 3 episodes of Major Depression-need medication indefinitely  Patients with risk factors: residual symptoms, ongoing psychosocial stressors, family history of mood disorder, the severity of prior episodes  Presence of psychosis in prior episodes and suicidal risk  In general the same medications and dose should be used as in acute and continuation phases  Relapse and recurrence of symptoms can still recur in up to 25% of patients

Discontinuation  Treatment can be discontinued if maintenance is not indicated.  The highest rate of relapse is 2 months after discontinuation of medications. Close monitoring should be done in this period.  Always taper and be aware of discontinuation symptoms, which may mimic depressive symptoms: disturbance of mood, energy, sleep and appetite