Anxiolytics.pptx

ANXIOLYTICS (ANXIETY DISORDERS, OBSESSIVE COMPULSIVE AND RELATED DISORDERS) Martha Agbeli, DNP, PMHNP-BC Revised-August 2023 The Anxiety Disorders  Specific phobia  Social anxiety disorder  Panic disorder  Agoraphobia  Generalized anxiety disorder  Separation anxiety disorder Anxiety Sx and Br...

ANXIOLYTICS (ANXIETY DISORDERS, OBSESSIVE COMPULSIVE AND RELATED DISORDERS) Martha Agbeli, DNP, PMHNP-BC Revised-August 2023 The Anxiety Disorders  Specific phobia  Social anxiety disorder  Panic disorder  Agoraphobia  Generalized anxiety disorder  Separation anxiety disorder Anxiety Sx and Brain Circuits fear - panic - phobia cortico-striatalthalamic-cortical circuit worry - anxious misery apprehensi on expectation - obsessions amygdalacentered circuit Neurotransmitters ↑ NE ↓GABA ↓Serotonin Anxiety Disorder Symptoms fatigue psychomotor concentration anxiety worry sleep panic attacks phobic avoidanc e compulirritability muscle sions tension anxiety disorders Anxiety: Friend or Foe?  Anxiety is a natural response  “Fight or Flight”  Can be protective  Can also be maladaptive – when?  When the response is triggered excessively, inappropriately, or the anxiety itself causes impairment  A good, thorough history and assessment is essential Anxiety Disorders Etiology: 1. Defects in the Limbic system, midline brain and sections of the cortex 2. Hyperactivity of the autonomic NS( ↑BP, diaphoresis, tremors, pupil dilation, ↑HR ↑RR) 3. Neurobiological deficits = ↓ levels of GABA ; ↑NE. ***Firstline treatment = SSRI for chronic anxiety, GAD, Panic disorder  Treat comorbid depression  Lack abuse risk  Low side effect rate Knowledge Check  NOTE: Venlafaxine (Effexor) can be very activating (patients can be restless)  Medical conditions that may precipitate anxiety (DM, Thyroid disease, seizure, COPD etc.) BENZODIAZEPINES Anxiety disorders Muscle spasms Common Indications Seizures Sleep disorders ETOH withdrawal etc. Anesthesia induction Benzodiazepines Alprazolam and Lorazepam are commonly prescribed MOA: Potentiate effects of GABA (Remember GABA is inhibitory)→drowsiness, cognitive impairment, dampening of fear and anxiety, impaired balance, moto control, muscle tone and coordination, anterograde amnesia. Elderly patients: Increased fall risk, hip fracture risk Enhance activity of GABA at GABA-A receptor  Potential for abuse and addiction  Patient become physical dependent and build tolerance  Can be used to treat Akathisia  Choice of BDZ depends on time of onset, duration of action and method of metabolism (OTL= Outside The Liver( Lorazepam, Oxazepam, Temazepam)= not metabolized by the liver  S/E: Anticholinergic, unusual behaviors, hallucinations, daytime drowsiness, amnesia Benzodiazepine use in anxiety disorders  Useful in the initial weeks of SSRI/SNRI initiation to rapidly reduce anxiety. Note: Patients tend to discontinue the antidepressant when co-prescribed a rapidly effective benzodiazepine. Caution with patient w/ a hx of substance abuse, personality disorder or chronic pain → high risk of abuse and misuse. Benzodiazepine Withdrawal = like ETOH withdrawal  Insomnia  Anxiety  Hand tremors  Irritability  Anorexia  Nausea/vomiting  Autonomic hyperactivity (diaphoresis, tachycardia, HTN)  Tonic –clonic seizures = life threatening Note: Abrupt abstinence after chronic use can be life threatening.  Taper ~ 10% total dose/week  “Physical and behavioral taper”  Common strategy to convert from SA to LA to facilitate more comfortable taper Knowledge Check  Benzodiazepine withdrawal symptoms (insomnia, anxiety, hand-tremors, irritability, anorexia, nausea/vomiting, autonomic hyperactivity (diaphoresis, tachycardia, hypertension), tonic-clonic seizure (life-threatening) Examples of Available Benzodiazepines Benzodiazepine class  Short acting  Midazolam (Versed)  Triazolam (Halcion)  Not used as anxiolytics  Alprazolam (Xanax, Niravam)  Oxazepam (Serax)  Intermediate acting  Lorazepam (Ativan)  Temazepam (Restoril)  Estazolam (ProSom)  Clonazepam (Klonopin) intermediate/long  Long acting  Chlordiazepoxide (Librium)  Clorazepate (Tranxene)  Diazepam (Valium)  Flurazepam (Dalmane) Short Acting = < 6hrs Intermediate Acting (6half life 20 hours half life Quick acting (for seizure For insomnia, anxiety disorders, Panic attacks) Long Acting (> 20 hours half life) (Moderate-Severe anxiety) Good for ETOH withdrawal Midazolam (Versed) Used in medical and surgical settings Lorazepam (Ativan) Txt panic attacks, ETOH and sedative-hypnotic detox Used with Haldol for acute agitation Diazepam (Valium)= Used in GAD, severe ETOH withdrawal and seizures Rapid onset Less commonly prescribed for anxiety d/t Euphoria Alprazolam (Xanax) Hight potential for abuse d/t short half life (rapid onset) Oxazepam(Serax) ETOH and sedativehypnotic detox Clonazepam (Klonopin) Avoid in renal dysfunction Longer half life- 1-2x daily dosing Temazepam (Restoril) Chlordiazepoxide (Librium) - High potential for S/E: Drowsiness, Impaired gaitdependence (especially in elderly); anterograde amnesia, confusion, rebound insomnia Flurazepam NOTE: Benzodiazepine Overdose: Give Flumazenil to reverse effects (it competes w/ benzodiazepines at the central synaptic GABA receptor sites) Benzodiazepines Generic/Brand Dose Range Half-life Rate of onset Chlordiazepoxide 15-40mg / Librium 20-110 hours Intermediate Diazepam/ Valium 15-40mg 30-100 hours Fast Clonazepam/ Klonopin 0.5-4mg 20-50 hours Intermediate Lorazepam/ Ativan 1-6mg 14 hours Intermediate Oxazepam/ Serax 15-120mg 9 hours Slowintermediate Alprazolam/ Xanax 1-4mg 14 hours intermediate Benzos: Key Takeaways  Easy to start  Hard to stop Tolerance Abuse Addiction Treatment-interfering “It’s the only thing that works” (sometimes very true, other agents won’t quite work or feel the same way)  Physical dependence      Knowledge Check Which has the Highest anticholinergic effect= Benzo vs. TCA vs. SSRIs (TCAs have the highest anticholinergic effect, benzos have some, SSRIs have the least) Note: Treatment for acute panic attacks = can use benzo short term in addition to. Long-term SSRI Known limitation of Benzo txt= rebound insomnia Benefits of benzodiazepines as compared to antidepressants NON-BENZO ANXIOLYTICS Non-Benzo Anxiolytics Buspirone (Buspar) Partial agonist at 5HT1A = ↓serotonergic activity Slower onset of action than typical benzos (i.e. takes several weeks) Augmentation: Often used in combination with another agent (e.g. SSRI) Low potential for abuse/addiction Dosed 2-three times per day NO PRN Hydroxyzine(Atarax) An antihistamine =anticholinergic s/e Quick acting = for patients who cannot take Benzos *See next slide for more details* Barbiturates (e.g Phenobarbital) Propranolol (Inderel) Rarely used d/t lethality of overdose, significant withdrawal potential, potential for abuse and side effect profile Beta blocker Used off-label Useful for panic attacks and performance anxiety related effects (i.e. palpitations, sweating and tachycardia Also used for Akathisia S/E: Bradycardia, hypotension Beta blockers can be fatal in a cocaine overdose Contraindicated in asthma or COPD d/t bronchospasm risk Patients with comorbid substance use – consider nonaddictive anxiolytic alternatives e.g. gabapentin and Antihistamines with anxiolytic properties (e.g. diphenhydramine or hydroxyzine) Antihistamines  Hydroxyzine (pamoate = Vistaril, capsules; hydrochloride = Atarax, tablets)        Fairly wide dosage range Individuals respond quite differently to different doses For some, 12.5mg is not tolerated, for others 50mg is minimally effective Generally start at 25mg once or twice daily, sometimes splitting tablet in half for lower dose Sedating (can help with sleep) Sometimes weight gain, sometimes paradoxical response Again, better if “benzo naïve” Anticonvulsants  Gabapentin (“PRN” or scheduled) (works on voltage-sensitive Ca2+ channels, not GABA)  Pregabalin  Tiagabine  Sometimes lamotrigine, oxcarbazepine (as scheduled)  Gabapentin most frequently used in this class, but does now have “street value” Knowledge Check  MOA of Buspirone (Buspar) = Does it cause dependence? (partial serotonin agonist (5HT1A), weak affinity for 5HT2, weak D2 antagonist, low potential for addiction) RECAP Anxiety disorders and management Disorder Psychopharmacologic management Agoraphobia –intense fear of being in public places where escape or obtaining help may be difficulty CBT and SSRIs Generalized anxiety disorder e.g. Lexapro; Paxil; Cymbalta; Effexor 1st line= SSRIs 2nd line= Buspar, SNRI Can consider short term course of Benzos or augmentation with buspirone (Buspar) Panic attacks Initially use Benzos Panic disorder e.g. Prozac, Paxil; Zoloft; Effexor; clomipramine, imipramine 1st line = SSRI, SNRIs 2nd line= TCAs= though limited use Adjunct= Benzos (USE WITH CAUTION, short-term until other meds reach therapeutic efficacy Alprazolam(Xanax)= FDA approved for Panic d/o Social Phobia (e.g. Performance anxiety)– fear of scrutiny by others or fear of acting in humiliating or embarrassing way e.g. CBT 1st line = SSRI or SNRIs Benzos can be used as scheduled or PRN Beta blockers such as atenolol (50-100mg) and propranolol (2040mg) 1 hour before performance or public speaking Specific Phobia Luvox, Paxil, Zoloft, Effexor, CBT w/ exposure Obsessive Compulsive Disorder (OCD) Obsesionas and/or compulsiones that are time consuming, distressing and impairing. e.g. Prozac, Luvox, Paxil, Zoloft, Clomipramine, Meds + CBT 1st line= SSRI (often need high doses of Zoloft, Prozac); Luvox 2nd line = SNRI (e.g. Venlafaxine) (Clomipramine=Anafranil) Can augment with atypical antipsychotic in severe cases ECT in debilitating, treatment resistant cases Knowledge Check  What are the symptoms for SSRI discontinuation syndrome (FINISH) (flu like symptoms (aches, pains, chills), insomnia, nausea, imbalance, sensory disturbance (tremors, sensation of electrical shock), hyperarousal)  A patient experiencing SSRI related sexual dysfunction= switch to Wellbutrin  First line agent for anxiety disorders? E.g. Social anxiety disorder (SAD)  Signs of Serotonin Syndrome; muscle spasms, fever, racing heart, headache, and confusion  Only tricyclic antidepressant (TCA) thought to be effective in the treatment of obsessive-compulsive disorder (OCD) (clomipramine (Anafranil) due to its high serotonin selectivity)  Treatment options for various anxiety disorders (e.g. performance anxiety)  Management of Generalized anxiety disorder