Panic disorder SSRIs

Panic disorder SSRIs Venlafaxine XR Alprazolam Clomipramine Clonazepam Imipramine Phenelzine... 

Panic disorder SSRIs, TCAs, MAOIs, benzodiazepines... 

FIGURE 69-2. Algorithm for the pharmacotherapy of panic disorder. SSRI = selective serotonin reuptake inhibitor, BZ = benzodiazepine. (Compiled from Bandelow et al, Work Group on Panic Disorder, Ballenger et al, and Sheehan. )... 

For panic disorder, tricychc antidepressants and MAO inhibitors, as well as high-potency benzodiazepines (notably alprazolam, clonazepam, and lorazepam) (see Chapter 16), are effective in blocking the autonomic expression of panic itself, thereby facilitating a comprehensive rehabilitation program. Imipramine and phenelzine are well-studied antidepressants for panic disorder. SSRIs also may be effective, but /3 adrenergic receptor antagonists, buspirone, and low-potency benzodiazepines usually are not, and bupropion can worsen anxiety. 

Beginning in the 1960s, ben2odia2epiae anxiolytics and hypnotics rapidly became the standard prescription dmg treatment. In the 1980s, buspkone [36505-84-7] (3), which acts as a partial agonist at the serotonin [50-67-9] (5-hydroxytryptamine, 5-HT) type lA receptor, was approved as treatment for generali2ed anxiety. More recently, selective serotonin reuptake inhibitors (SSRIs) have been approved for therapy of panic disorder and obsessive—compulsive behavior. 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

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. 

SSRIs are first-line agents, but BZs are the most commonly used drugs for panic disorder. 

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. 

The current SSRIs in the United States inclnde fluoxetine, fluvoxamine, sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro). All effectively treat major depression. In addition, one or more of the SSRIs has been shown effective in the treatment of dysthymic disorder, the depressive phase of bipolar disorder, premenstrual dysphoric disorder, panic disorder, social phobia, obsessive-compnlsive disorder, bnlimia nervosa, and binge-eating disorder. 

Monoamine Oxidase Inhibitors (MAOIs). Shortly after their introduction, MAOIs, snch as phenelzine (Nardil), were found to reduce the frequency of panic attacks. It became a standard treatment for what is now known as panic disorder nntil snpplanted by the benzodiazepines and SSRIs. Although all MAOIs are presumably effective for panic disorder, phenelzine is the best studied and has been shown to be effective at daily doses ranging from 45 to 90 mg. When used to treat panic disorder, phenelzine should be initiated at a dose of 15mg/day and gradually increased in 15 mg increments until reaching a therapeutic dose. 

Like the MAOIs, TCAs are hindered by a delayed onset of action that can be especially intolerable for those with frequent and severe panic attacks. When starting treatment, TCAs, like SSRIs, may also produce a transient nervousness that is especially uncomfortable for those with panic disorder. When this occurs, the starting dose should be reduced by half, and the pace of subsequent dose increases should be even slower than usual. Because they produce prominent side effects and can be dangerous in overdose, TCAs are also now reserved for patients unresponsive to other treatments. Refer to Chapter 3 for a more extensive discussion of the TCAs. 

Newer Generation Antidepressants. All SSRIs have been shown effective in the treatment of panic disorder. Of these, flnoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft), as well as the SNRI venlafaxine ER (Effexor XR), have received FDA approval for the treatment of panic disorder. Because they are safer and easier to tolerate, SSRls/SNRls have largely supplanted the MAOIs and TCAs as standard treatments (along with benzodiazepines) for panic disorder. 

As noted earlier, SSRIs/SNRIs can produce transient nervousness during the start-np phase of treatment. A start low and go slow approach is therefore advisable when treating patients with panic disorder. Nevertheless, panic disorder is often best controlled only after attaining daily doses at the upper end of the dose range. Please refer to Chapter 3 for additional discussion of the SSRIs/SNRIs. 

The hrst-line treatments for panic disorder are (1) cognitive-behavioral therapy (CBT), (2) benzodiazepines, and (3) SSRIs/SNRls. Each of these three treatment modalities can be nsed independently or in combination. The selection of the primary treatment depends on several factors inclnding severity and frequency of the panic attacks, comorbid illnesses, and patient preference. 

In addition to their proven efficacy in the treatment of all types of depression, the SSRIs have been shown to be the drugs of choice in the treatment of panic disorder, obsessive-compulsive disorder, bulimia nervosa, and as an adjunct to the treatment of alcohol withdrawal and relapse prevention, premenstrual dysphoric disorder and post-traumatic stress disorder. The usefulness of these drugs in treating such a diverse group of disorders reflects the primary role of serotonin in the regulation of sleep, mood, impulsivity and food intake. 

Long-term use The effectiveness of long-term use of SSRIs for OCD, panic disorder, and bulimia has not been systematically evaluated. However, the long-term use of SSRIs for depression has been evaluated and demonstrated to maintain antidepressant response for up to 1 year. 

In recent years many of these primary care cases that would formerly have been seen as anxiety disorders have been portrayed as anxious-depressives and have led to treatment with antidepressants, in particular the more recent serotonin reuptake inhibitors. As part of this rebranding a variety of states such as panic disorder, post-traumatic stress disorder, social phobia and generalized anxiety disorder have appeared, along with more traditional disorders such as obsessive compulsive disorder (OCD). Many of these diagnoses are likely to lead to prescriptions of an SSRI although the evidence for benefit from SSRIs is poor except for OCD. 

SSRI/SNRI GAD OCD Panic disorder PTSD Social anxiety disorder Onset worsening side-effects on initiation few long-term effects Relatively safe in overdose (venlafaxine possibly less safe) Well-described more common with paroxetine uncommon with fiuoxetine... 

Frank JB, Kosten TR, Giller EL Jr, Dan E (1988) A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder. Am J Psychiatry 145 1289-1291 Goddard AW, Brouette T, Almai A, Jetty P, Woods SW, Charney D (2001) Early coadministration of clonazepam with sertraline for panic disorder. Arch Gen Psychiatry 58 681-686 Goodnick PJ, Goldstein BJ (1998) SSRIs in affective disorders. I. Basic pharmacology. J Psychopharmacol 12(Suppl B) S5-S20... 

Of the SSRIs, fluoxetine has been studied most extensively. Birmaher et al. (1994) and Fairbanks et al. (1997) both found significant improvement in various anxiety disorder symptoms in typically developing children. Fluoxetine was also found to be effective in the treatment of selective mutism (Black and Udhe, 1994 Dummit et ah, 1996). Fluoxetine has also been studied in individuals with MR and autistic disorder. In an open trial. Cook et al (1992) found that fluoxetine was associated with significant improvement in the Clinical Global Impression (CGI) severity ratings in 15 of 23 individuals (65%) with autistic disorder and in 10 of 16 individuals (62%) with MR. All of the SSRIs appear to have similar properties and have been approved for panic disorder, phobias, OCD, and anxiety disorder. Sertraline has been approved for treatment of PTSD, and paroxetine, for social phobia. 

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