Anxiety& Depression in Primary Care- a Pharmacology Primer. Lisa Deloris Slade, DNP, MSN, FNP-BC North Carolina NP Spring Symposium March 27, 2017

Transcription

1 Anxiety& Depression in Primary Care- a Pharmacology Primer Lisa Deloris Slade, DNP, MSN, FNP-BC North Carolina NP Spring Symposium March 27, 2017

2 Objectives Describe pharmacology, treatment considerations, appropriate use and effective evaluation of anti- anxiety medications Describe pharmacology, treatment considerations, appropriate use and effective evaluation of anti-depression medications Define pharmacology, treatment considerations, appropriate use and effective evaluation of anti-insomnia medications

3 ANXIETY Definition-Facts-Statistics An abnormal and overwhelming sense of apprehension and fear often marked by physiological signs, by doubt concerning the reality and nature of the threat, and by self-doubt about one s capacity to cope with the threat. Most common mental illness in the US affecting 40 million adults Causes can include organic mental illness and/or external factors External factors may include: Stress at work, Stress at school, Stress in a personal relationship, Financial stress, Stress from emotional trauma, Stress from a serious medical illness, Side effect of medication, Use of an illicit drug, symptom of a medical illness, or a lack of oxygen Generalized Anxiety Disorder, Panic, Social Anxiety Disorder, Specific Phobias, Post-Traumatic Stress Disorder

4 ANXIETY Symptoms of Anxiety Disorders Feelings of panic, fear, and uneasiness Problems sleeping Cold or sweaty hands and/or feet Shortness of breath Heart palpitations An inability to be still and calm Dry mouth Numbness or tingling in the hands or feet Nausea Muscle tension Dizziness

5 ANXIETY Current Treatment Guidelines FIRST LINE TREATMENT Serotonergic antidepressant or Cognitive behavioral therapy Grade 1A Medications: SSRI or SNRI paroxetine, sertraline, citalopram, escitalopram, venlafaxine ER, and duloxetine Duration: At least 12 months

6 ANXIETY Current Treatment Guidelines (cont.) SECOND LINE TREATMENT Tricyclic Antidepressants amitriptyline, amoxapine, chlordiazepoxide/amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, perphenazine/amitriptyline, protriptyline, trimipramine Benzodiazepines Short-acting: alprazolam, midazolam, oxazepam, triazolam Mid-acting: estazolam, lorazepam, temazepam Long-acting: chlordiazepoxide, chlordiazepoxide/amitriptyline, clonazepam, clorazepate, diazepam, flurazepam, clobazam

7 ANXIETY Current Treatment Guidelines (cont.) Treatment-Resistant Generalized Anxiety Disorder Cognitive Behavioral Therapy in addition to SSRIs Mirtazapine Quetiapine

8 SSRIs - Pathophysiology Monoamine Theory of Depression. Image copied from 04/10/2016

9 Serotonin Syndrome Too Happy? Mild symptoms: diarrhea, nausea, vomiting, headache, shivering, agitation, restlessness, lack of coordination, and confusion Adjust dosing Check other medications for interactions Severe symptoms: all of the above, high fever, irregular heartbeat, loss of consciousness, seizures Stop medication Emergency treatment as indicated

10 ANXIETY Tricyclic Antidepressants chlordiazepoxide/amitriptyline (Limbitrol/Limbitrol DS) Schedule IV - maximum 5 refills in six months Non-CS: amitriptyline, despiramine, imipramine, nortriptyline, doxepin, clomipramine Black Box Warning: Suicidality risk increased in children, adolescents and young adults with major depressive or other psychiatric disorders Avoid abrupt withdrawal Adverse Reactions: orthostatic hypotension, hypertension, syncope, ventricular arrhythmias, QT prolongation, torsade's de pointe, AV block, MI, stroke, seizures, extrapyramidal symptoms, ataxia, others Drug Interaction Characteristics: anticholinergic effects, CNS depression, hyperprolactinemic effects, hypertensive effects, hyponatremia, hypotensive effects, lowers seizure threshold

11 ANXIETY TCA (cont.) Safety Monitoring: Pregnancy Category D, need therapeutic drug levels: ng/ml toxic > 500 ng/ml days to achieve steady state; maximum efficacy may take 6 weeks to achieve Monitor serum drug levels; EKG if CV disease; CBC, LFTs if prolonged treatment and SI

12 ANXIETY Benzodiazepines Short-acting {half-life 11.2 hours} Alprazolam (Xanax, Xanax XR, Niravam) Midazolam (Versed) Oxazepam (Serax) Triazolam (Halcion) Mid-acting {half-life 14 hours} Estazolam Lorazepam (Ativan) Temazepam (Restoril)

13 ANXIETY Benzodiazepines (cont.) Long-acting {half-life hours} Chlordiazepoxide (Librium) Chlordiazepoxide/Amitriptyline (Limbitrol, Limbitrol DS) Clonazepam (Klonopin, Klonopin Wafers) Clorazepate (Tranxene SD, Tranxene T) Diazepam (Valium) Diazepam Auto Injector Flurazepam (Dalmane) Clobazam (Onfi)

14 ANXIETY Benzodiazepines (cont.) Schedule IV maximum 5 refills in six months No Black Box Warning Cautions: Pulmonary, renal, hepatic impairment, elderly and those with depression Avoid abrupt withdrawal withdrawal symptoms will occur Drug interactions may cause CNS depression Pregnancy Category D Monitor LFTs in prolonged treatment

15 ANXIETY Benzodiazepines (cont.) Benzodiazepines, due to their widespread availability, are recreationally the most frequently used pharmaceuticals. This accounts for approximately 35% of all drug-related visits to hospital emergency and urgent care facilities. Alprazolam (Xanax) is the most common benzodiazepine for recreational use followed by clonazepam, lorazepam, and diazepam. It is highly recommended for a person with a benzodiazepine addiction to seek medical aid at a benzodiazepine detox center. The withdrawal effects are comparable to that of barbiturates and alcohol withdrawal and are directly associated with how long someone has had a benzodiazepine dependency. The severity of the withdrawal is directly dependent on the dosage strength, length of use, dosage frequency, previous use of cross-tolerant or crossdependent drugs, and the manner in which the dosage is reduced. The withdrawal process can be lethal due to its tendency to provoke withdrawal convulsions. The withdrawal symptoms are often typified by psychosis, sleep disturbance, anxiety, dry retching and nausea, panic attacks, memory problems, hallucinations, seizures and possibly suicide

16 BENZODIAZPINES Mechanism of Action

17 BENZODIAZEPINES

18 DEPRESSION Definition-Facts-Statistics Mood disorder that causes a persistent feeling of sadness and loss of interest 6.9% of adults in the U.S. 16 million had at least one major depressive episode in the past year. There is no single cause of depression. Brain chemistry, hormones, and genetics may all play a role. Other risk factors for depression include: low self-esteem, anxiety disorder, borderline personality disorder, post-traumatic stress disorder (PTSD), physical or sexual abuse, chronic diseases like diabetes, multiple sclerosis, or cancer, alcohol or drug abuse, certain prescription medications, family history of depression Major depression (includes grief), Persistent depressive, Bipolar, Seasonal Affective, Postpartum, Psychotic

19 DEPRESSION Symptoms Feelings of sadness or emptiness that don t go away within a few weeks may be a sign of depression. extreme irritability over minor things anxiety and restlessness anger management issues loss of interest in favorite activities fixation on the past or on things that have gone wrong thoughts of death or suicide

20 DEPRESSION Symptoms (cont.) insomnia or sleeping too much debilitating fatigue increased or decreased appetite weight gain or weight loss difficulty concentrating or making decisions unexplained aches and pains In children, depression may cause clinginess and refusal to go to school. Teens may be excessively negative and begin avoiding friends and activities. Depression may be difficult to spot in older adults. Unexplained memory loss, sleep problems, or withdrawal may be signs of depression.

21 DEPRESSION Current Treatment Guidelines First line (initial) Pharmacotherapy plus psychotherapy SSRIs (preferred) No use of Controlled Substances

22 DEPRESSION Current Treatment Guidelines (cont.) Refractory Depression May add second antidepressant of different class Refer to specialist Our general order in choosing an antidepressant: Selective serotonin reuptake inhibitor Serotonin-norepinephrine reuptake inhibitor Atypical antidepressants Serotonin modulator Tricyclic antidepressant Monoamine oxidase inhibitor

23 DEPRESSION Current Treatment Guidelines (cont.) General order in choosing an adjunctive medication is as follows: Second-generation antipsychotic Lithium Thyroid hormone Second antidepressant from a different class

24 Depression Cyclic Anti-depressants Despite the increasing popularity of the selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression, CAs continue to play an important role in the treatment of enuresis, obsessive-compulsive disorder, attention deficit hyperactivity disorder, school phobia, and separation anxiety in the pediatric population. In adults, indications for CAs include depression, neuralgic pain, chronic pain, and migraine prophylaxis. Some of the more commonly prescribed CAs include amitriptyline, desipramine, imipramine, nortriptyline, doxepin, clomipramine, and protriptyline. Maprotiline, a tetracyclic compound, and amoxapine, a dibenzoxapine, are newer compounds that have a slightly different structure and toxicologic profile.

25 INSOMNIA Definition-Facts-Statistics A persistent disorder that can make it hard to fall asleep; hard to stay asleep or both; despite the opportunity for adequate sleep. The National Institutes of Health estimates that roughly 30 percent of the general population complains of sleep disruption. Most common sleep disorder in the United States Previously viewed as a sleep disturbance secondary to a medical condition, psychiatric illness, sleep disorder or medication. Now recognized as often an independent disorder. Acute insomnia versus Chronic insomnia (at least three nights per week for at least three months)

26 INSOMNIA Definition-Facts-Statistics (cont.) Differential diagnosis to consider in evaluation of sleep disturbance: Psychiatric conditions: Depression, Anxiety, Substance Abuse, Post-traumatic stress Medical conditions: Pulmonary (COPD,Asthma), Rheumatologic (Arthritis, FMS, Chronic pain), Cardiovascular (Heart failure, Ischemic heart disease, Nocturnal angina, Hypertension), Endocrinologic (Hyperthyroidism), Urinary (Nocturia), Gastrointestinal (GERD), Diabetes, Cancer, Menopause, Lyme Disease, AIDS, Chronic fatigue syndrome, Dermatologic, Neurological conditions: Neurodegenerative (Alzheimer, Parkinson s), Painful peripheral neuropathies, Hemispheric and brainstem strokes, Brain tumors, Traumatic brain injury, Headache syndromes, Fatal familial insomnia

27 INSOMNIA Definition-Facts-Statistics (cont.) Medications: CNS stimulants, CNS depressants, Bronchodilators, Antidepressants, Beta agonists, Glucocorticoids Other sleep disorders: Restless leg syndrome, Willis-Ekbom disease, Periodic limb movement disorder, sleep-disordered breathing, Circadian rhythm disorders,

28 INSOMNIA Current Treatment Guidelines Behavioral Therapy including sleep hygiene, stimulus control, relaxation techniques, sleep restriction therapy, cognitive therapy and cognitive behavioral therapy for insomnia Medications: Non-benzodiazepine sedatives, Melatonin agonists, Antidepressants, & Benzodiazepines. Combination therapy can be used: 6-8 weeks of medication alongside behavioral therapy with gradual withdrawal of medication.

29 INSOMNIA Benzodiazepines Schedule IV; no more than 5 refills in 6 months Estazolam Flurazepam (Dalmane) Lorazepam (Ativan) Temazepam (Restoril) Triazolam (Halcion) Avoid abrupt withdrawal; No black box warning; AE: angioedema, respiratory depression, seizures, suicidality; CNS depression; Pregnancy category X; monitor LFTs if prolonged treatment

30 INSOMNIA Non-Benzodiazepines Eszopiclone (Lunesta) 1-3 mg po q HS Zolpidem (Ambien, Ambien CV, Edular, Zolpimist, Intermezzo) Zaleplon (Sonata) No black box warning; avoid abrupt withdrawal; avoid alcohol use; AE: depression exacerbation, suicidal ideation, aggression, hallucinations; CNS depression; Pregnancy Cat C; no routine testing Butalbital (Butisol) mg po q HS short term No black box warning; avoid abrupt withdrawal; AE: apnea, respiratory depression; CNS depression, increases thyroid hormone clearance; Pregnancy Cat D; monitor CBC, LFTs, Bun/CR Secobarbital (Seconal) Schedule II Never prescribe!!!!!!

31 INSOMNIA Treatment Considerations Risks of pharmacologic therapy include side effects, as well as physical and psychological addiction with long-term use. These risks may be increased in certain clinical settings: Pregnancy Sedative-hypnotics may increase the risk of fetal malformations if used during the first trimester. Alcohol consumption Sedative-hypnotics should not be combined with alcohol because there is a risk of excessive sedation and respiratory suppression whenever central nervous system suppressants are combined. Renal or hepatic disease Most sedative-hypnotic medications undergo hepatic and renal clearance. Metabolic clearance may be delayed in patients who have renal or hepatic disease, leading to accumulation and excessive sedation. Pulmonary disease or sleep apnea Many sedative-hypnotics are respiratory suppressants that can worsen obstructive sleep apnea or hypoventilation. Nighttime decision makers Sedative-hypnotics should not be taken by individuals who may be called upon to make important decisions during the night (eg, clinicians on-call or single parents responsible for the care of young children) because they can cause excess sedation and impair decision-making. Older adults The risk of adverse effects is increased in older adults, especially those who are older than 75 years. This is a consequence of multiple comorbidities and central nervous system changes associated with aging.

32 INSOMNIA Treatment Considerations Most clinicians select a sedative-hypnotic on the basis of the type of insomnia (ie, sleep onset or sleep maintenance) and the duration of effect: For patients with sleep onset insomnia, a short-acting medication is a reasonable choice for an initial trial of pharmacologic therapy. This may improve the insomnia with less residual somnolence the following morning. Examples of short-acting medications (duration of effect 8 hours) include Zaleplon zolpidem, triazolam, lorazepam, and ramelteon. For patients with sleep maintenance insomnia, a longer-acting medication is preferable for an initial trial of pharmacologic therapy. Examples of longer-acting medications include zolpidem extended release, eszopiclone, temazepam, estazolam, and low dose doxepin. However, these medications may increase the risk for hangover sedation and patients must be warned about this possibility. For patients with awakening in the middle of the night, both zaleplon and a specific sublingual tablet form of zolpidem have been developed for use during the night, with the constraint that there will be at least four hours of time in bed remaining after administration.

33 References Anxiety and Depression. (2015) Retrieved from Craig, C. & Stitzel, R. Modern Pharmacology with Clinical Applications, Sixth Edition. (2004) Baltimore, MD: Lippincott, Williams & Wilkins. Golan, D., Tashjian, A., Armstrong, E., & Armstrong, A. (2012). Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, Second Edition Philadelphia, PA: Lippincott, Williams & Wilkins. McHenry, L., & Salerno, E. (2003). Pharmacology in Nursing. St. Louis, MO: Mosby Inc. Mechanism of Action: Benzodiazepines (2016). Image retrieved from Pathophysiology of SSRI (2016). Image retrieved from