Choosing an antidepressant: How to think like a shrink

1. Choosing an antidepressant:How to think like a shrink March 26th, 2013 Jessica Nittler MD Stephanie Bagby-Stone MD

2. Goals and Objectives *Review all antidepressants, side effects and mechanisms of action *Understand why to choose certain antidepressants, changing doses, switching or augmenting *Understand which antidepressants are safe to give during pregnancy

3. Selective Serotonin Reuptake Inhibitors - SSRIs • The first line of treatment for depression is an SSRI. • Fluoxetine (Prozac) Sertraline (Zoloft) • Paroxitine (Paxil) Citalopram (Celexa) • Escitalopram (Lexapro) Fluvoxamine (Luvox) • All SSRIs have generally the same level of effectiveness in the treatment of depression and choices are often made based upon side effect profiles, half-lives, past response to a particular medication by the patient or the patient’s close relative or cost. • Side effects are generally mild and related to gastrointestinal problems, sometimes sleep problems, and sexual side effects. • SSRIs can take 4 to 6 weeks to see improvement in symptoms. • At times, they can induce mania in individuals with that predisposition. Care should be given in individuals with a strong family history of Bipolar. • Black box warning - Care also should be given to issues associated with potential suicidal ideation and behavior.

4. Serotonin-Norepinephrine Reuptake Inhibitors - SNRIs Venlafaxine (Effexor) • A combination selective serotonin reuptake inhibitor and noradrenergic reuptake inhibitor, also works on dopamine at higher doses. • serotonin norephinephrine dopamine • Generally well tolerated and side effects similar to SSRIs. • Can take 4 to 6 weeks to see improvement in symptoms. • May increase diastolic blood pressure at higher doses. • May also be helpful for hot flashes in women Desvenlafaxine (Pristiq) Duloxetine(Cymbalta) • A combination selective serotonin reuptake inhibitor and noradrenergic reuptake inhibitor. • serotonin = norephinephrine • Lower potential for sexual side effects. • Can take 4 to 6 weeks to see improvement in symptoms.

5. Case of the Suffering Senior • A 22 year old female student with history of panic attacks returns from spring break and reports a relapse despite having been doing well for many months. She has been feeling much worse with restlessness, poor sleep, dizziness, headache and shock-like sensations. She denies any recent stressors. • What might be going on?

6. Serotonin Discontinuation Syndrome • FLUSH • Flu-like symptoms of fatigue, myalgias, loose stools, nausea, diaphoresis • Light headedness/dizziness • Uneasiness/restlessness • Sleep disturbance and sensory disturbances • Including shock like electrical sensations • Headache Effexor, Paxil, Luvox > Zoloft, Lexapro, Celexa > Prozac

7. Tricyclic Antidepressants - TCAs • TCAs are equally efficacious and are as effective as SSRIs for depression. • Imipramine (Tofranil) Nortriptyline (Pamelor) • Amitriptyline (Elavil) Clomipramine (Anafranil) • They all work in varying degrees on the norepinephrine and serotonin systems but each to a different degree and with a different level of specificity for a particular neurotransmitter. • Can take 4 to 6 weeks to see improvement in symptoms. • Side effects and other considerations • TCAs generally have a high potential for side effects like sleepiness, weight gain, dry mouth, constipation, blurred vision, urinary retention, tachycardia, etc. • TCAs also generally cause an increase in the time interval associated with the QRS complex as measured with an EKG. This can lead to dangerous arrhythmias during the course of treatment. • TCAs are lethal in overdose with as little as a one week supply. • TCAs are also prescribed for issues of pain related to fibromyalgia, chronic fatigue, migraine headache, etc.

8. Case of the Sad Sorority Sister • A 19 year old female freshman presents to your office for help with depression, anxiety and stopping “bad habits”. She already saw her physician at home to try Zyban for smoking cessation because it worked for her dad’s depression. During the interview you discover that she has been binging and purging daily for many years and also has episodes of binge drinking but has not told anyone about these issues before. • What concerns do you have for this patient?

9. Buproprion (Wellbutrin) • Buproprion (Wellbutrin SR or XL, Zyban) is effective in the treatment of depression, seasonal affective disorder and smoking cessation and works via norepinephrine and dopamine. • Wellbutrin can be activating and increase anxiety, irritability or cause sleep problems. • Fewer sexual side effects. • Less likely to inducing “switching” to mania • Can take 4 to 6 weeks to see improvement in symptoms. • Avoid use in individuals that have a history of head injury, seizure disorder or bulimia. These individuals may be at higher risk for seizure on this medication. • Newer formulations (SR and XL forms) have lengthened the half-life of the medication and this is believed to lessen the risk of seizure in individuals and improve compliance due to less frequent dosing.

10. Other Antidepressants • Mirtazipine (Remeron) • Somnolence, weight gain, dizziness, dry mouth, constipation • Less likely to cause sexual side effects • Desyrel (Trazodone) • Sedation, orthostatic hypotension, HA • Mostly used for insomnia • Viibryd (Vilazodone) • Less likely to cause sexual side effects • Weight neutral • GI side effects most common (diarrhea, nausea, vomiting) • Mostly works as SSRI with 5-HT1a receptor partial agonist • MAOIs (Nardil, Parnate, Emsam patch) • Helpful for “atypical” depression • Dietary restriction of tyramine containing foods to avoid adrenergic hypertensive crisis (aged meat and cheeses, wine, yogurt, fava beans, chocolate, excessive caffeine…) • Numerous dangerous drug-drug interactions (SSRIs, tramadol, stimulants, phenylalanine, dextromethorphan, mepirirdine…) • Long wash out period

11. Adjunctive Medications • Other medications have been used as adjuncts to those listed above when treating depression • Adjunctive antidepressants • Buspar • Mood stabilizers (eg lithium or valproic acid) • Thyroid hormone                • Stimulants • Atypical antipsychotics • Light Therapy-10,000 lux for 30 minutes in the morning.

12. Recommendations for Switching and Tapering Tapering Sertraline-taper by increments of 50mg Citalopram-taper by increments of 20mg Escitalopram-taper by 10mg increments Paroxetine-taper by increments of 20mg Fluoxetine-taper by increments of 20mg-can go faster due to longer half-life Switching If switching from one SSRI to another or SNRI, easy to transition and don’t always need to cross taper If switching from SSRI to Buproprion, taper SSRI

13. Antidepressants and drug-drug interactions

14. Case of Side Effect Sally 19 y/o sophomore referred to psychiatry after trial of three SSRI’s. Common complaints of “not feeling better” When asked about specific problems with medications she indicated she had HA’s with each one, nausea with one, dizziness with another. What should you consider next?

15. Side effect management Try low dose Citalopram or Buspar. Citalopram 5-10mg Buspar 5-10mg Consider Bupropion. Many patients that complain of side effects, seem to be related to serotonin. Consider lower than normal starting doses of the agent.

16. Strategies for Treatment-Resistant Depression

17. Shrink Think - Choosing an antidepressant • Past history of response • If a patient responded well to a medication in the past it would be a good choice to begin again. • If a previous medication didn't work or had side effects it is generally good to avoid it. However, it was not a treatment failure if it was not an adequate dose for adequate duration. “the past repeats itself” • Family history of response • If a parent, sibling or other biological relative has responded well to a particular medication, it is would be a good choice. “your brain chemistry is similar to your family’s brain chemistry” • Patient preference • If a patient believes that a medication works well for someone they know, and if there isn't a contra-indication , it could be a good option. There is some power to believing something will help. • Similarly, if patient reports that someone they knew had bad side-effects or acted weird on a certain medication, consider picking something else. “go with the power of belief”

18. Shrink Think - Choosing an antidepressant • Financial Considerations • This may be the only consideration if the patient is uninsured and paying cash for the meds. • Begin what's cheapest that will work and won't cause intolerable side effects. • If the patient has been on something and had good success, then loses their insurance, try something cheaper in the same class of medication. “money matters” • Medical Issues • Avoid medications that might exacerbate an existing medical conditions. • Wellbutrin is contraindicated in patients with seizure disorders, eating disorders, or a history of CNS lesions, so don't start it in these patients. • Effexor can cause diastolic hypertension at higher doses. • Drug-Drug Interactions • Avoid starting medications that interact with what the patient's already on. • Prozac and Paxil causes 2D6 interactions • Luvox effects1A2-metabolized drugs • Serzone effects 3A4-metabolized drugs “know your cyp450 interactions”

19. Shrink Think - Choosing an antidepressant • Symptoms & Side Effects • Know what is most important to the patient. • Then consider receptors and neurotransmitters. • Poor appetite—histamine • Low concentration—dopamine • Low energy—norepinephrine • Tired and unmotivated— Wellbutrin • Lots of OCD symptoms—SSRI • Concurrent pain syndrome— Cymbalta or TCA • Weight loss—Remeron “know your neurotransmitters” “what is side effect for some is a benefit for others”

20. Treatment of Depression in Pregnancy Inconclusive data at this point. Most antidepressants are Category C, except Paxil is Category D (CHM). American Journal of Psychiatry, May 2009, showed risk of continuous untreated depression and exposure to SSRI’s during pregnancy both result in 20% risk of preterm birth weight. Consider Omega-3 Fatty Acids. Safe in Pregnancy and can be helpful in mild to moderate depression. Also consider psychotherapy for mild to moderate depression.

21. Treatment of Depression in Pregnancy Mayo Clinic outline, December 2009 APA-ACOG Algorithm for Treatment of Depression during Pregnancy Adequately treat depression Psychotherapy recommended for mild to moderate depression ECT is also an option for severe depression Women with MDD, recurrent, severe who stop meds are at high rate for relapse Women with severe depression, acute suicidality, psychosis or bipolar disorder should be referred to a psychiatrist.

22. Questions?\Discussion