Panic disorder discontinuation

In two studies in which benzodia2epines were gradually tapered, concurrent cognitive-behavioral therapy (CBT) did not increase the proportion of patients who were able to successfully discontinue their use of these agents (Oude Voshaar et al. 2003 Vorma et al. 2003). On the other hand, other studies of patients with panic disorder found that CBT facilitated the discontinuation of benzodiazepine use (Otto et al. 1993). Similarly, CBT may be superior to supportive medical management in preventing the reoccurrence of panic attacks in panic disorder patients in whom alprazolam has been tapered (Bruce etal. 1999). 

Bruce TJ, Spiegel DA, Hegel MT Cognitive-behavioral therapy helps prevent relapse and recurrence of panic disorder following alprazolam discontinuation a longterm follow-up of the Peoria and Dartmouth studies. J Consult Clin Psychol 67 151-156, 1999... 

Otto MW, Pollack MH, Sachs GS, et al Discontinuation of benzodiazepine treatment efficacy of cognitive-behavioral therapy for patients with panic disorder. Am J... 

The acute phase of panic disorder treatment lasts about 12 weeks and should result in marked reduction in panic attacks, ideally total elimination, and minimal anticipatory anxiety and social anxiety avoidance. Treatment should be continued to prevent relapse for an additional 12 to 18 months before attempting discontinuation. 

The initial dose of SSRI is similar to that used in depression. Patients should be titrated as tolerated to response. Many patients will require maximum recommended daily doses. Patients with comorbid panic disorder should be started on lower doses (Table 37-4). When discontinuing SSRIs, the dose should be tapered slowly to avoid withdrawal symptoms, with the possible exception of fluoxetine. Relapse rates may be as high as 50%, and patients should be monitored closely for several weeks.58 Side effects of SSRIs in SAD patients are similar to those seen in depression and most commonly include nausea, sexual dysfunction, somnolence, and sweating. 

Patients with panic disorder should be seen every 2 weeks during the first few weeks to adjust medication doses based on symptom improvement and to monitor side effects. Once stabilized, they can be seen every 2 months. The Hamilton Rating Scale for Anxiety (score less than or equal to 7 to 10) can be used to measure anxiety, and the Sheehan Disability Scale (with a goal of less than or equal to 1 on each item) can be used to measure for disability. During drug discontinuation, the frequency of appointments should be increased. 

SSRIs are initiated at doses similar to those used for depression (see Table 68-13). If there is comorbid panic disorder, the SSRI dose should be started at one-fourth to one-half the usual starting dose of antidepressants. The dose should be tapered slowly during discontinuation to decrease the risk of relapse. 

Maintenance Phase Treatment. Because panic disorder tends to be a chronic condition, the appropriate duration of therapy is a critically important question. Conventional practice is to continue treatment for 6-9 months after remission has been achieved and then to taper medicines gradually over several weeks to months. The relapse rate is extremely high with over one-half of those treated with medications alone experiencing a relapse within a few months of discontinuing treatment. There is some evidence that CBT may reduce this relapse rate. When relapse occurs, it is usually advisable to restart the medication that was previously used. 

Rickels K, Schweizer E (1998) Panic disorder long-term pharmacotherapy and discontinuation. J Clin Psychopharmacol 18 12S-18S... 

In a randomized, double-blind, placebo-controlled study of paroxetine treatment of panic disorder in adults, 12 weeks of treatment was followed by 2 weeks of placebo (Oehrberg et ah, 1995). In this placebo period, 19 patients out of 55 (34.5%) who had received paroxetine reported an adverse event on discontinuation, compared to 7 out of 52 (13.5%) patients who had received placebo. The most common discontinuation complaint was dizziness. 

Being a chronic condition, panic disorder is likely to require long-term treatment. Current clinical practice tends to favor a trial of medication for at least 3 months, with continuation for 6-12 months if there is a good clinical response, ffowever, the most appropriate time to discontinue therapy has not yet been determined, and more data from long-term follow-up studies are needed [Ballenger 1992). Clinical experience indicates that 40% of patients with panic disorder may need treatment for a year, and some 20%-40% may require continued maintenance treatment thereafter (Keller and ffanks 1993). 

A second issue relating to long-term medication is the effect of withdrawing medication at the end of a period of treatment. Benzodiazepines are associated with discontinuation symptoms, and their repeated use may foster the development of true physiological dependence. In a study of discontinuation of treatment for panic disorder [Rickels et al. 1993) with either alprazolam [n = 27), imipramine [n = 11) or placebo [n = 10), a withdrawal syndrome was observed in almost all patients treated with alprazolam but in few pa-... 

Ballantine HT, Bouckoms AJ, Thomas EK, et al Treatment of psychiatric illness by stereotactic cingulotomy. Biol Psychiatry 22 807-819, 1987 Ballenger JC Medication discontinuation in panic disorder. J Chn Psychiatry 53 (suppl) 26-31, 1992... 

Holland RL Fluvoxamine in panic disorder after discontinuation Neuropsychopharmacology 10 102S, 1994... 

A trial comparing daily doses of 50,100 and 200 mg sertraline with placebo for 12 weeks in patients with panic disorder. No consistent evidence of a dose response effect was found because all three doses of sertraline produced significant efficacy compared with placebo and, surprisingly, there was no significant between-dose difference with regard to discontinuations due to adverse events (Asheikh et ul., 2000). 

A larger set of placebo-controlled studies show conclusively that imipramine is also effective for the treatment of panic disorders. Other agents shown to be effective in panic disorders include the SSRIs paroxetine, sertraline, fluvoxamine, fluoxetine and citalopram. Generally, initial treatment of moderate to severe panic disorders may require the initiation of a short course of benzodiazepines e.g. clonazepam (0.5 1 mg twice daily), and an SSRI. The patient will obtain immediate relief from panic attacks with the benzodiazepine whereas the SSRI may take 1 6 weeks to become effective. Once a patient is relieved of initial panic attacks, clonazepam should be tapered and discontinued over several weeks and SSRI therapy continued thereafter. There are no pharmacological treatments available for specific phobias, however controlled trials have shown efficacy for several agents, e.g. phenelzine, moclobemide. clonazepam, alprazolam, fluvoxamine. sertraline and paroxetine in the treatment of social phobia (Roy-Byrne and Cowlev, 2002). 

TABLE 13-3. Symptoms reported with discontinuation of aiprazoiam treatment for panic disorder... 

Pecknold JC, Swinson RP, Kuch K, et al. Alprazolam in panic disorder and agoraphobia results from a multicenter trial. III. Discontinuation effects. Arch Gen Psychiatry 1988 45 429-436. 

Burrows GD, Norman TR, Judd FK, et al. Short-acting versus long-acting benzodiazepines discontinuation effects in panic disorders. J Psychiatr Res 1990 24[Suppl 2] 65-72. 

Rosenbaum JF, Moroz G, Bowden CL. Clonazepam in the treatment of panic disorder with or without agoraphobia a dose-response study of efficacy, safety, and discontinuance. Clonazepam Panic Disorder Dose-Response Study Group. J Clin Psychopharmacol 1997 17 390-400. 

Moroz G, Rosenbaum JF. Efficacy, safety, and gradual discontinuation of clonazepam in panic disorder a placebo-controlled, multicenter study using optimized doses. J Clin Psychiatry 1999 60 604-612. 

Anxiety is a common complaint that invariably complicates addictive illnesses. Estimates of co-morbid anxiety and alcohol disorders range from 20% to 50%, with men more likely to self-medicate anxiety than women (453, 454 and 455). Some investigators have also found increased rates of alcoholism in family members of patients with anxiety disorders (456, 457). Patients with alcohol or drug dependence show a tendency for development of panic disorder earlier, and it has been suggested that repeated alcohol withdrawal may be the trigger for panic attacks in susceptible individuals ( 458, 459). Finally, BZDs, the primary pharmacological treatment for these disorders, are themselves addictive and sometimes associated with anxiety syndromes, especially on their discontinuation ( 460). 

Currently, many physicians adopt a benzodiazepine-sparing strategy by using benzodiazepines when necessary but conservatively. That is, benzodiazepines can often be helpful when treatment is initiated or when a rapid-onset therapeutic effect is desired. They can also help improve the short-term tolerability of SSRIs by blocking the jitteriness and exacerbation of panic sometimes observed when initiating treatment with an SSRI or other antidepressant. Benzodiazepines can also be useful to top up the patient s treatment on an as-needed basis for sudden and unexpected decompensation or short-term psychosocial stressors. Finally, if a patient is not fully responsive to an antidepressant or combinations of antidepressants, long-term treatment with concomitant benzodiazepines and antidepressants may become necessary to effect full or adequate control of symptoms. Sometimes, once symptoms are suppressed for several months to a year, the benzodiazepine can be slowly discontinued and the patient maintained long-term on the antidepressant alone. The consequences of inadequate treatment of panic disorder can be very severe loss of social and oc-... 

Alprazolam has been researched more extensively than any other benzodiazepine in panic disorder, and is very effective. Because of its short duration of action, it generally must be administered in three to five daily doses. Clonazepam, which has a longer duration of action than alprazolam, has also been investigated in panic disorder. It can generally be administered twice a day. Clonazepam is reported to have less abuse potential than alprazolam and to be easier to taper during discontinuation owing to its longer half-life. 

Unfortunately a large percentage of patients relapse when medications are discontinued—as many as 70 percent have a return of panic symptoms if medications are withdrawn a year after treatment is initiated. Panic disorder, thus, appears to be an often chronic condition. To date, there are no very long-term follow-up studies tracking the course of this disorder. However, for practical purposes, the clinician should anticipate medication treatment lasting at least one year. Then a trial discontinuation or medication reduction can be implemented to determine if continued treatment is necessary. 

Because of the chronicity of illness, persons with GAD and panic disorder are at high risk of developing benzodiazepine dependence. Benzodiazepine dependence is a physiologic phenomenon demonstrated by the appearance of apredictable abstinence syndrome (withdrawal symptoms) on abrupt discontinuation of therapy. Withdrawal symptoms may result because of the sudden dissociation of a benzodiazepine from its receptor site. After abrupt discontinuation, an acute decrease in GABA neurotransmission results, producing a less inhibited CNS. 

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