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Page 1 of 3 PSYCHIATRY 2 ANXIETY DISORDERS – TREATMENT DR. LOS BANOS 2.1a AUGUST 14, 2014 Bautista, Cruz, Gillera, Janolo, Merilles I. Antidepressants II. Benzodiazepines III. Alpha-delta Ca Channel Blocker IV. Beta Blocker V. Azapirones DRUGS USED FOR ANXIETY ANTIDEPRESSANTS SSRI/SNRI TCA MAOIs Efficacy First line treatment for anxiety disorders Similar with SSRI in Panic disorders and Generalized anxiety disorders; may work if first line agents do not Excellent option for severe tx resistant anxiety disorder; effective for Panic disorders and Generalized anxiety disorders Potency for Abuse Low Low Low Overdose Safer Lethal Greatest safety burden of all antidepressants Side Effects More tolerable; mild and transient Nausea, diarrhea, HA, insomnia, jitterness, restlessnes s, diminished sexual interest, SUICIDE Less tolerable side effects Dry mouth, blurred vision, constipation, urinary retention, cardiac arrythmis postural hypotension, dizziness Worst profile Serotin Syndrome Gain weight loss sleep feel sedated during the day BENZODIAZEPINES  2nd line of treatment  Same efficacy and tolerability with TCA  Used for potent short-term effects  Help reduce anxiety while waiting for SSRI to take effect  All sedative-hypnotics cross the placental barrier during pregnancy. If sedative-hypnotics are given during the predelivery period, they may contribute to the depression of neonatal vital functions. Sedative-hypnotics are also detectable in breast milk and may exert depressant effects in the nursing infant.  MOA: o Augmentation of GABA activity produces enhanced neuronal inhibition, which manifests as sedation and hypnosis. Chloride channels open in response to GABA activation, this leads to hyperpolarization and decrease neuronal firing. BZD increase the frequency of channel opening  Advantages: o Rapid onset of action o Relatively high therapeutic index plus availability of flumazenil o Low risk of drug interactions o Minimal effects on CV and autonomic functions  Effects: o Anterograde amnesia o Psychomotor and cognitive functions o Rebound anxiety upon Discontinuation  Dependence and Withdrawal o Involuntary or Iatrogenic o Voluntary  BDZs available in the Philippines: o Diazepam o Alprazolam o Clonazepam BDZ Latency Duration DIAZEPAM Valium Dosage: 5-20 mg daily Cost: P9.15 tablet/day Rapid onset Long acting Less rebound symptoms Withdrawal reactions may be delayed In acute alcohol withdrawal, Valium may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. ALPRAZOLAM Xanor Dosage: 0.25-0.5 mg TID Cost: P19.78 per tablet x 3 = P59.34 day Rapid onset Short acting More rebound anxiety Withdrawal reactions Better sedative/hypnotic Preferred over long- acting in elderly CLONAZEPAM Rivotril Dosage: 0.25-2 mg BID Cost: P1002 per tablet x 2= P10.02 per day Rapid onset Long acting Less rebound symptoms Withdrawal reactions may be delayed GENERALIZED ANXIETY DISORDER  Alprazolam showed positive results in placebo and active comparator-controlled studies.  Diazepam, in turn, was found to be effective in studies containing a placebo condition as well as studies using a comparator with established efficacy.  WFSBP guidelines have rated both compounds with a category of evidence ‘‘A’’ (which is the highest).  Lorazepam was the drug associated with the highest percentage of study withdrawals. (Dell’osso & Lader, 2013) OBSESSIVE-COMPULSIVE DISORDER  In a double-blind, randomized, parallel, placebo-controlled study, when clonazepam was added to sertraline, it showed no additional benefit.  Clonazepam did not evidence any superiority suggesting that it is likely not effective as monotherapy in treating OCD. (Dell’osso & Lader, 2013) SOCIAL ANXIETY DISORDER  BZDs (clonazepam, in particular) to be efficacious compounds in SAD in that they work rapidly, they are well- tolerated and that thet may be particularly useful for individuals with episodic performance-related social anxiety. o However, they do not find favour it as first-line medications because of their limited spectrum of action, potential withdrawal difficulties as well as limited amount of data in the prevention of relapse
Page 2 of 3 PSYCHIATRY 2 Anxiety Disorders - Treatment 2.1a August 14,2014 Bautista, Cruz, Gillera, Janolo, Merilles POST-TRAUMATIC STRESS DISORDER  The available evidence does not support the use of BZDs as monotherapy in PTSD (Class ‘‘F’’ for WFSBP guidelines) and doubts persist on the potential benefit in combination therapy. PANIC DISORDER  Most robust evidence of BZD efficacy in the short-term treatment  Many trials have been conducted with alprazolam, clonazepam, diazepam and lorazepam, which have attested to the short-term efficacy of these compounds in assuaging the core symptoms of PD. SLEEP DISORDERS  BZDs and related BZD-receptor agonists, however, are the most effective pharmacological therapies for insomnia. ALPHA–DELTA CALCIUM CHANNEL BLOCKER  Anticonvulsant  Reduce neuronal excitability  Resemble BDZ  Fewer problems with abuse, tolerance and withdrawal  Treatment for stimulant and alcohol dependence BETA BLOCKERS  Use as single dose agents for performance-related anxiety AZAPIRONES  Used for Generalized Anxiety Disorder, the only anxiety disorder where there is consistent efficacy
Page 3 of 3 PSYCHIATRY 2 Anxiety Disorders - Treatment 2.1a August 14,2014 Bautista, Cruz, Gillera, Janolo, Merilles This trans is brought to you by: Special reports of Ms. Afalla and Ms. Leynes References: Dell’osso, B. & Lader, M. (2013). Do benzodiazepines still deserve a major role in the treatment of psychiatric disorders? A critical appraisal. European Psychiatry. 28: 7-20. doi: 10.1016/j.eurpsy.2011.11.003. Farach, F., Pruitt, L., Jun, J., Jerud, A., Zoellner, L. & Roy-Byrne, P. (2012). Pharmacological treatment of anxiety disorders: current treatment and future directions. Journal of Anxiety Disorders. 26: 833-843. Retrieved from http://dx.doi.org/10.1016/j.janxdis.2012.07.009 Katzung, B., Masters, S. & Trevor, A. (2012). Basic and Clinical Pharmacology. Singapore: McGraw-Hill Companies, Inc. Nash, J. & Nutt, D. (2007). Psychopharmacology of anxiety. Psychiatry. 6:4.

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