Pearls for practitioner's: Anti-depressants, Anxiolytics and ...

Pearls for practitioner's: Anti-depressants, Anxiolytics and ...

PEARLS FOR PRACTITIONER'S: ANTI-DEPRESSANTS, ANXIOLYTICS AND HISTORY TAKING AMY NEWSTROM, CNP NURSE PRACTITIONER ASSOCIATION OF SOUTH DAKOTA ANNUAL CONFERENCE 2016 LEARNING OBJECTIVES Discuss importance of history taking in regards to psychotropic medications Increase understanding of commonly used anti-depressants: mechanism of action, side effects, and titration Increase understanding of commonly used anxiolytics: mechanism of

action, side effects, and titration Discuss referral points Discuss alternative therapy: Transcranial Magnetic Stimulation HISTORY TAKING & CHOOSING THE RIGHT MEDICATION Identify the symptoms the client wants treated Listen for a clear history Know medical background In general, the first line

treatment for depressive symptoms, in the absence of mood instability, is selective serotonin reuptake inhibitors (SSRI) TARGETED SYMPTOMS OF ALL ANTIDEPRESSANTS Depressed mood Sleep disturbance Appetite disturbance

Fatigue Decreased sexual drive Psychomotor agitation or retardation Impaired concentration Loss of ability to experience pleasure (anhedonia) Atypical depression is depression exhibited by hypersomnia, hyperphagia, low energy and mood reactivity SELECTIVE SEROTONIN REUPTAKE INHIBITORS

SELECTIVE SEROTONINS REUPTAKE INHIBITORS (SSRIS) Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac) Fluvoxamine (Luvox) Paroxetine (Paxil) Sertraline (Zoloft) COMMON SIDE EFFECTS OF SSRIS

Sexual dysfunction Decreased spontaneity (emotional flattening) Weight gain Diarrhea Initial increase in anxiety Insomnia Tremors Headache Dizziness SEROTONIN NOREPINEPHRINE REUPTAKE INHIBITORS:

Same as SSRI but acting on norepinephrine and serotonin SEROTONIN NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS) Atomoxetine (Strattera) Desvenlafaxine (Pristiq) Duloxetine (Cymbalta) Levomilnacipran (Fetzima) Milnacipran (Savella)

Venlafaxine (Effexor) COMMON SIDE EFFECTS OF SNRIS NAUSEA VOMITING CONSTIPATION HYPERHIDROSIS TACHYCARDIA ERECTILE DYSFUNCTION URINARY HESITANCY OR RETENTION SEDATION

HYPONATREMIA INCREASE IN BLOOD PRESSURE NOREPINEPHRINE DOPAMINE REUPTAKE INHIBITOR BUPROPION (WELLBUTRIN) Often used as an augmenting agent Can reduce fatigue Off label use for ADHD Frequently abused No sexual side effects

ALPHA 2 ANTAGONIST: MIRTAZAPINE (REMERON) DUAL SEROTONIN AND NOREPINEPHRINE AGENT Notable side effects: -dry mouth -constipation -increased appetite/ weight gain -hypotension -flu-like symptoms -change in urinary function

SEROTONIN PARTIAL AGONIST REUPTAKE INHIBITOR (SPARI): VILAZODONE (VIIBRYD) Onset of action may be sooner than other SSRIs Essentially same side effects as SSRI but less potential for sexual side effects and weight gain First member of this new antidepressant class MULTIMODAL ANTI-DEPRESSANT VORTIOXETINE (BRINTELLIX)

May have less sexual side effects Shown effective specifically in elderly patients with depression Long half life Can be costly STAR*D STUDY (SEQUENTIAL TREATMENT ALTERNATIVES TO RELIEVE DEPRESSION) Took place over a 7 year period and enrolled 4,041 outpatients. 1,165 participants were excluded, leaving 2,876 outpatients, ages 18-75 from 41 clinical sites around the United States. Patients were referred to the trial by their doctor and all were diagnosed with Major Depressive Disorder (NIH, 2016)

4 levels of treatment: -Level 1: Citalopram for 12-14 weeks -Level 2: Divided into the switch or add-on groups -Level 3: Divided into the switch or add-on groups -Level 4: Considered to have treatment-resistant depression National Institute of Mental Health (2006) https://www.psychologytoday.com/blog/mad-in-america/201008/the-stard-scandal-new-paper-sums-it-all THE EMPIRIC APPROACH TO DIAGNOSING BIPOLAR DISORDER Many patients have never had full mania Many patients have poor recollections of past mood states

Bipolar is a current fad and may influence patient recollection Patient may like their hypomania and dislike their depression, whereas spouse may like the patients depression and dislike their hypomania Diagnosis often has more to do with reconstructing past history than assessing current symptoms Everybody has a temperament and a personality but not all are pathological PRESENTATION IN CLINICAL PRACTICE: BIPOLAR I Percent Time Spent in Symptom Categories % Time (Hypo)manic

% Time Cycling/Mixed 9.3 5.9 31.9 52.7 % Time Depressed Judd et al. Arch Gen Psychiatry 2002.

% Time Asymptomatic PRESENTATION IN CLINICAL PRACTICE: BIPOLAR II Percent Time Spent in Symptom Categories % Time Pure Hypomanic % Time Cycling/Mixed 1.3 2.3

50.3 % Time Pure Depressed 46.1 % Time Asymptomatic Judd et al. Arch Gen Psychiatry 2003.

ASKING THE RIGHT QUESTIONS Symptom history Ask patient about any hypomanic symptoms immediately before or after depressed period Ask patient if others have noticed any symptoms of mania spectrum Dont just focus on moodconsider over-activity as a core feature Behavior history Ask about impulsive behaviors, divorce/separation, job changes Akiskal et al. J Affect Disord 2000. Bowden. Psychiatr Serv 2001.

DIAGNOSTIC ISSUES FOR DEPRESSION: IS IT UNIPOLAR OR BIPOLAR? In a survey of 600 bipolar patients, more than 1/3 of respondents sought help within one year of symptom onset 69% were not diagnosed as bipolarmost frequent diagnosis was major depression Mean physicians consulted before correct Dx: 4 1/3 did not receive a bipolar diagnosis for 10 years WERE THEY MISDIAGNOSED OR DID THEY PROGRESS TO BIPOLAR DISORDER? Hirschfeld et al. J Clin Psychiatry 2003.

STATISTICAL SIGNIFICANCE A Swedish national cohort study found that people (both women and men diagnosed with bipolar disorder died approximately 9 years earlier than the general population (Crump, Sandquist, Winkleby, & Sundquist, 2013). Both genders had an 8-10 fold increase risk of suicide (Crump, Sandquist, Winkleby, & Sundquist, 2013). The lifetime prevalence of alcohol misuse in bipolar I disorder is 34.1%: One out of five women and two out of five men (DiFlorio, Craddock, & van de Bree, 2014).

BENZODIAZEPINES Symptoms targeted by benzodiazepines: *Anxiety *Insomnia *Agitation *Withdrawal BENZODIAZEPINES: HOW THEY WORK Facilitate the binding of GABA to GABA A receptors (GABA agonist) Facilitates the flow of chloride into the neuron to decrease excitability Alprazolam (Xanax)

Lorazepam (Ativan) Chlordiazepoxide (Librium) Midazolam (Versed) Clonazepam (Klonopin) Oxazepam (Serax) Diazepam (Valium)

Quazepam (Doral) Estazolam (Prosom) Temazepam (Restoril) Flurazepam (Dalmane) Triazolam (Halcion) BENZODIAZEPINES: COMMON SIDE

EFFECTS BUSPIRONE (BUSPAR) A serotonin 1A partial agonist FDA approved for management of anxiety disorders Usually well-tolerated Side effects can include: dizziness, headache, nervousness, sedation, excitement, nausea and restlessness Lack of dependence and withdrawal Lack of sexual dysfunction and weight gain

REFERRAL POINTS Mood instability Psychosis Treatment-resistant depression Questions of safety TRANSCRANIAL MAGNETIC STIMULATION Non-invasive option FDA approved for the treatment of Major Depressive Disorder in adult patients who have failed to achieve satisfactory improvement from one prior antidepressant

medication at or above the minimal effective dose and duration in the current episode (U.S. Food and Drug Administration, 2011). Works by applying a highly concentrated magnetic field, switched rapidly on and off, to the left prefrontal cortex. The left prefrontal cortex is thought to play a role in mood regulation. Magnetic fields concentrated in this area produce very small electric currents that reach 2-3 centimeters into the brain directly beneath the treatment coil. It is thought that the electrical currents activate cells that release neurotransmitters like serotonin, norepinephrine and dopamine to treat depression (Clinical TMS Society, 2016). RESOURCES

Akiskal, H.S., Bourgeois, M.L., Angst, J., Moller, H., Hirschfeld, R. (2000). Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. Journal of Affective Disorders, 59(Suppl 1). S5-S30. Bachhuber, M.A., Hennessy, S., Cunningham, C.O. and Starrels, J.L. (2016). Increasing benzodiazepine prescriptions and overdose mortality in the United States, 1996-2013. American Journal of Public Health, 106(4). 686-688. Bowden, C.L. (2001). Strategies to reduce misdiagnosis of bipolar depression. Psychiatric Services, 52(1). 51-55. Clinical TMS Society (2016). TMS Therapy. Retrieved on February 18, 2016 at http://www.clinicaltmssociety.org/left/clinicaltmssociety/ Crump, C., Sundquist, K., Winkleby, M.A., & Sundquist, J. (2013). Comorbidities and mortality in bipolar disorder: a Swedish national cohort study. Journal of the American Medical Association Psychiatry, 70(9). 931-939. DiFlorio, A., Craddock, N., & van de Breen, M. (2014). Alcohol misuse in bipolar disorder: A systematic review and meta-analysis of comorbidity rates, European Psychiatry, 29(3). 117-124. Frye, M.A., Gitlin, M.J. & Altchuler, L..L.. (2004). Unmet needs in bipolar depression. Depression and Anxiety, 19(4), 199-208.

Goldberg, J.F., Hansow, M. & Whiteside, J.E. (2001). Risk for bipolar illness in patients initially hospitalized for unipolar depression, American Journal of Psychiatry, 158(8), 1265-1270. Harvard Health Publication. (2010). Transcranial magnetic stimulation. Harvard Mental Health Letter, September 2010. Hirschfeld, R. M. et al. (2003). Screening for bipolar disorder in the community. Journal of Clinical Psychiatry, 64 (1), 53-59. Ingersol, E. & Rak, C. (2016). Psychopharmacology for mental health professionals: An integrative approach. (2nd Ed.). Boston, MA: Cengage Learning. RESOURCES Judd LL, Akiskal HS, Schettler PA, Coryell W, Endicott J, Maser JD, et al. (2003). A prospective investigation of the natural history of the longterm weekly symptomatic status of bipolar II disorder. Archives of General Psychiatry, 60. 261-269. National Institute of Mental Health. (2010). Magnetic Stimulation Scores Modest Success as Antidepressant. Retrieved on February 18, 2016 at http://www.nimh.nih.gov/news/science-news/2010/magnetic-stimulation-scores-modest-success-as-antidepressant.shtml National Institute of Mental Health. (2006). Questions and answers about for NIMH sequenced treatment alternatives to relieve depression

(STAR*D) study- all medication levels. Retrieved on September 14, 206 at http://www.nimh.nih.gov/funding/clinical-research/practical/stard/allmedicationlevels.shtml Rush. A. J. et al. (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. American Journal of Psychiatry, 163(11), 1905-1917. Scrandis, D.A. (2015). Identification and management of bipolar disorder. The Nurse Practitioner, 39(10). 31-37. Stahl, S.M. (2013). Stahls essential psychopharmacology: neuroscientific basis and practical applications. (4th Ed.). Cambridge, UK: Cambridge University Press. Stahl, S.M. (2014). Prescribers guide. (5th Ed.). Cambridge, UK: Cambridge University Press. U.S. Food and Drug Administration Center for Devices and Radiological (2011). Health Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Repetitive Transcranial Magnetic Stimulation (rTMS) Systems. Retrieved on February 22, 2016 at http://www.fda.gov/RegulatoryInformation/Guidances/ucm265269.htm Valente, S. & Fisher, D. (2012). Transcranial magnetic stimulation for major depression. The Journal of Chi Eta Phi Sorority, 56(1): 23-25.

Whitaker, R. (2010). The STAR*D scandal: a new paper sums it all up. Psychology Today. Retrieved on August 30, 2016 at https://www.psychologytoday.com/blog/mad-in-america/201008/the-stard-scandal-new-paper-sums-it-all World Health Organization. (2015). Depression: Fact Sheet No 369. Retrieved on February 22, 2016 at http://www.who.int/mediacentre/factsheets/fs369/en/. QUESTIONS

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