Major depression panic disorder with

When treating mild-to-moderate panic disorder, we recommend avoiding benzodiazepines in favor of CBT or antidepressants. Because CBT and antidepressants are both effective for panic disorder and major depression (commonly comorbid with panic disorder), the choice between the two largely rests on patient preference. Antidepressants are preferred for those who are pessimistic regarding the potential benefit of CBT, cannot afford CBT, or are unable (or unwilling) to invest the time necessary to complete a course of CBT. In our experience, some patients may accrue significant beneht from the combined treatment, particularly those with more moderate symptoms who struggle with the exposure aspects of therapy. 

The analysis of the relationship between panic disorder and major depression has produced conflicting results. The possible link between these disorders has been provided by the frequent occurrence of major depression in patients with panic disorder and agoraphobia, both... 

Studies of patients with panic disorder suggest that those who suffer from panic report having quality of life as poor as that of patients with major depression. Panic attacks and/or fear of panic attacks can interfere with the development of social relationships, personal happiness, and employment. 

Bakish D, Hooper CL, Filteau MJ, et al A double-blind placebo-controlled trial comparing fluvoxamine and imipramine in the treatment of panic disorder with or without agoraphobia. Psychopharmacol Bull 32 135-141, 1996 Bakish D, Hooper CL, Thorton MD, et al Fast onset an open study of the treatment of major depressive disorder with nefazodone and pindolol combination therapy. Int Clin Psychopharmacol 12 91-97, 1997 Baldwin DS Depression and sexual function. J Psychopharmacol 10 (suppl l) 30-34, 1996... 

Major depression with social withdrawal Panic disorder with agoraphobia Social phobia... 

Complicating the proper assessment and, by implication, the most appropriate therapy for many patients, is the very real possibility of neuropsychiatric syndromes that may mimic classic psychiatric disorders, exacerbate them, or coexist with such disorders as major depression, panic attacks, and brief reactive psychosis. Thus, the CNS may be affected by various primary malignancies or secondary metastases cardiovascular disorders, leading to ischemic episodes or hemorrhagic events and several HIV-related complications. 

Antidepressants tend to provide a more sustained and continuous improvement of the symptoms of attention-deficit/hyperactivity disorder than do the stimulants and do not induce tics or other abnormal movements sometimes associated with stimulants. Indeed, desipramine and nortriptyhne may effectively treat tic disorders, either in association with the use of stimulants or in patients with both attention deficit disorder and Tourette s syndrome. Antidepressants also are leading choices in the treatment of severe anxiety disorders, including panic disorder with agoraphobia, generalized anxiety disorder, social phobia, and obsessive-compulsive disorder, as weU as for the common comorbidity of anxiety in depressive illness. Antidepressants, especially SSRIs, also are employed in the management of posttraumatic stress disorder, which is marked by anxiety, startle, painful recollection of the traumatic events, and disturbed sleep. Initially, anxious patients often tolerate nonsedating antidepressants poorly (Table 17-1), requiring slowly increased doses. Their beneficial actions typically are delayed for several weeks in anxiety disorders, just as they are in major depression. 

Fyer AJ, Liebowitz MR, Gorman JM, et al Effects of clonidine on alprazolam discontinuation in panic patients a pilot study. J Clin Psychopharmacol 8 270—274,1988 Garvey MJ, Tollefson GD Prevalence of misuse of prescribed benzodiazepines in patients with primary anxiety disorder or major depression. Am J Psychiatry 143 1601-1603, 1986... 

Panic disorder patients are more likely to experience stimulantlike side effects than patients with major depression and should be initiated on lower doses of antidepressant than those that are used for depression or other anxiety disorders. 

Mendlewicz J, Papdimitriou G, Wilmotte J (1993) Family study of panic disorder comparison with generalized anxiety disorder, major depression and normal subjects. Psychiatr Genet 3 73-78... 

Panic disorder is comorbid with episodes of depression at some stage in the majority of cases (Stein et al. 1990), with social anxiety disorder and to a lesser extent GAD and PTSD, and with alcohol dependence and personality disorder. Comorbidity results in increased severity and poor response to treatment. Panic disorder is associated with a significantly increased risk of suicide, and this is increased further by the presence of comorbid depression (Lepine et al. 1993). 

While no data on the role of 3a-reduced neuroactive steroids in PTSD or its treatment in panic disorder patients have been pubhshed to date, opposite changes to those seen in major depression have emerged. At baseline, patients with panic disorder had significantly increased concentrations of the positive allosteric modulators 3a,5a-THP and 3a,5P-THP, together with sig-... 

StrOhle A, Pasini A, Romeo E, Hermann B, Spalletta G, di Michele F, Holsboer F, Rupprecht R (2000) Fluoxetine decreases concentrations of 3a,5a-tetrahydrodeoxycorticosterone (3a,5a-THDOC) in major depression. J Psychiatr Res 34 183-186 StrOhle A, Kellner M, Holsboer F, Wiedemann K (2001) Anxiolytic activity of atrial natriuretic peptide in patients with panic disorder. Am J Psychiatry 158 1514-1516 StrOhle A, Romeo E, di Michele F, Pasini A, Yassouridis A, Holsboer F, Rupprecht R (2002) GABAA receptor modulatory neuroactive steroid composition in panic disorder and during paroxetine treatment. Am J Psychiatry 159 145-147 StrOhle A, Romeo E, di Michele F, Pasini A, Hermann B, Gajewsky G, Holsboer F, Rupprecht F (2003) Induced panic attacks shift GABAA receptor modulatory neuroactive steroid composition. Arch Gen Psychiatry 60 161-168 Szapiro G, Vianna MRM, McGaugh JL, Medina JH, Izquierdo I (2003) The role of NMDA glutamate receptors, PKA, MAPK, and CAMKII in the hippocampus in extinction of conditioned fear. Hippocampus 13 53-58... 

Biederman, J., Faraone, S.V., Biederman, J., Faraone, S.V., Hirshfield-Becker, D.R., Friedman, D., Rotin, J.A., and Rosenbaum, J.F. (2001) Patterns of psychopathology and dysfunction in high-risk children of parents with panic disorder and major depression. Am J Psychiatry 158 49-57. 

An empirical literature on combined treatment is just beginning to emerge. Randomized controlled trials in adults with panic disorder (Barlow et ah, 2000) and major depression (Keller et ah, 2000) suggest advantages for combined drug and cognitive-behavioral... 

A number of epidemiological studies [including several reviewed in May and Lichterman 1993] have shown that panic disorder and unipolar depression occur more commonly together than could be explained by chance. Some 50%-70% of patients with panic disorder also have major depression [J. Johnson et al. 1990 Volrath and Angst 1989]. The association also holds true for seasonal depression [Halle and Dilsaver 1993] and to some extent for bipolar disorders [Savino et al. 1993]. 

One analysis (Angst and Wicki 1993) showed agoraphobia in 2.6% of control subjects, 2.8% of subjects with major depression, 7.4% of subjects with pure panic, and 28.0% of subjects with both panic disorder and major depression. Similarly, the attempted suicide rate was 3.5% among control subjects, 5.0% in subjects with pure panic, 13.0% in subjects with depression without panic, and 28.9% in patients with both panic disorder and major depression. These data underline the importance of recognizing and treating comorbid depression in patients with panic disorder. 

Panic disorder is emerging from decades of comparative neglect as an apparently intractable and poorly understood condition to become the focus of intensive interest in epidemiological, pharmacological, and clinical research. Panic disorder is a chronic and distressing condition with a profound effect on the quality of life, similar to or even worse than the effect of major depression [Markowitz et al. 1989 Weissman 1991). Effective and well-tolerated treatment that can be used safely in the long term is badly needed. 

Gorman JM, Kent JM SSRls and SNRls broad spectrum of efficacy beyond major depression. J Chn Psychiatry 60 (suppl 4 33-38, 1999 Gorman JM, Papp LA Respiratory physiology and panic, in Neurobiology of Panic Disorder. Edited by BaUenger JC. New York, Alan R Dss, 1990 Gorman JM, Debowitz MR, Eyer AJ, et al Treatment of social phobia with atenolol. J Chn Psychopharmacol 5 298-301, 1985... 

Grunhaus L Clinical and psychobiological characteristics of simultaneous panic disorder and major depression. Am J Psychiatry 145 1214-1221, 1988 Grunze H, Walden J, Wolf R, et al Combined treatment with lithium and nimodipine in a bipolar 1 manic syndrome. Prog Neuropsychopharmacol Biol Psychiatry 20 419-426, 1996... 

Keller MB, Hanks DL Course and outcome in panic disorder and depression. J Clin Psychopharmacol Biol Psychiatry 17 551-570, 1993 Keller MB, Shapiro RW Double depression superimposition of acute depressive episodes on chronic depressive disorders. Am J Psychiatry 139 438-442, 1982 Keller MB, Shapiro RW, Lavori PW, et al Recovery in major depressive disorder analysis with the life table and regression models. Arch Gen Psychiatry 39 905-910, 1982a... 

Metz A, Shader Rl Combination of fluoxetine with pemoline in the treatment of major depressive disorders. Int Clin Psychopharmacol 6 93-96, 1991 Metz A, Evoniuk G, De Veaugh-Geiss J Multicentre trial of a S-HTj antagonist, ondansetron, in panic disorder [abstract). Paper presented at the 33rd annual meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico, 1994, p 165... 

Odagaki Y, Koyama T, Matsubara S, et al Effects of chronic lithium treatment on serotonin binding sites in rat brain. J Psychiatr Res 24 271-277, 1990 O Dwyer AM, Lightman SL, Marks MN, et al Treatment of major depression with metyrapone and hydrocortisone. J Affect Disord 33 123-128, 1995 Oehrberg S, Christiansen PE, Behnke K, et al Paroxetine in the treatment of panic disorder a randomised, double-blind, placebo-controlled study. Br J Psychiatry 167(3)374-379, 1995... 

Van Praag HM, Asnis CM, Kahn RS, et al Monoamines and abnormal behavior a multi-aminergic perspective. Br J Psychiatry 157 723-734, 1990 van Valkenburg C, Akiskal HS, Puzantian V, et al Anxious depression clinical, family history and naturalistic outcome—comparison with panic and major depressive disorders. J Affect Disord 6 67-82, 1984... 

Targnm, S.D. Differential responses to anxiogenic challenge studies in patients with major depressive disorder and panic disorder. Biol. Psvchiatrv 28, 21-34, 1990. 

Finally, because patients with panic disorder and major depression are frequently sensitive to any adverse effects of antidepressants, it is generally advisable to start at a reduced dose and gradually adjust the dose to the usually effective level to achieve the intended benefit. 

Johnson and co-workers (41) found that the lifetime rate of suicide attempts with uncomplicated panic disorder was about 7%, which is consistently higher than that of the general population without a psychiatric disorder (i.e., about 1%). The researchers concluded that panic disorder, either uncomplicated or as a co-morbid illness, led to a risk of suicide attempts comparable with those of major depression ( co-morbid or uncomplicated). Their data were derived from the Epidemiologic Catchment Area Study, with a probability sample of more than 18,000 adults living in five United States communities. 

In a second review of these data, Weissman et al. ( 42) found that 20% of patients with panic disorder and 12% of those with panic attacks had made suicide attempts. These results could not be explained by the coexistence of major depression, nor the presence of alcohol or drug abuse. They concluded that panic disorder or attacks were associated with an increased risk of suicidal ideation and attempts. 

Benzodiazepines (BZDs) have been used for the treatment of depression because their sedative effects can reduce insomnia, agitation, and anxiety symptoms that frequently accompany depressed states. Considerable evidence also indicates that major depression may accompany panic and agoraphobic disorders ( 199, 200 and 201). When depression precedes the onset of panic disorder, clinical experience suggests a better response to antidepressants than to BZDs, although no studies have directly addressed this issue (202). Conversely, available evidence indicates that when depression occurs after the onset of panic disorder, treatment with either a BZD or a tricyclic may result in concomitant improvement of both the panic and depressive symptoms (198, 199, 200, 201,202 and 203). Depression, however, has been reported to be an adverse effect of BZD treatment. 

BZDs may exacerbate depression and possibly increase suicide risk. Case reports and clinical trials also indicate that BZD treatment of generalized anxiety and panic may result in emergence of depression (215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225 and 226). In some of these reports, depression is ill-defined, but in others, it met DSM-III criteria for a major depressive disorder, requiring treatment with an antidepressant ( 225, 226). Depression has been reported with a variety of BZDs (alprazolam, bromazepam, clonazepam, diazepam, lorazepam), but there is no evidence that one is more likely than another to cause or aggravate depressive illness. 

Some of the growth in antidepressant use may be related to the broad application of these agents for conditions other than major depression. For example, antidepressants have received FDA approvals for the treatment of panic disorder, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). In addition, antidepressants are commonly used to treat pain disorders such as neuropathic pain and the pain associated with fibromyalgia. Some antidepressants are used for treating premenstrual dysphoric disorder (PMDD), mitigating the vasomotor symptoms of menopause, and treating stress urinary incontinence. Thus, antidepressants have a broad... 

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