Deina S. Nemiary, MD; and Praveen J. Penagaluri, MD, are Psychiatry Residents, Psychiatry and Behavioral Sciences, Morehouse School of Medicine, Atlanta. Deirdre Evans-Cosby, MD, is Assistant Professor, Psychiatry and Behavioral Sciences, Morehouse School of Medicine.
Dr. Nemiary; Dr. Penagaluri; and Dr. Evans-Cosby have disclosed no relevant financial relationships.
The authors acknowledge John Gaston, MD, Program Director of the Psychiatry and Behavioral Sciences Department at Morehouse School of Medicine, for his constant support.
Address correspondence to: Deina S. Nemiary, MD: email@example.com.
A 49-year-old man with a diagnosis of mood disorder not otherwise specified (NOS) presented to the psychiatric emergency room with worsening depression, suicidal thoughts, severe anxiety, and increased intensity of self-injurious behaviors. The patient presented with depressed mood, feeling of hopelessness, anhedonia, easy fatigability, and problems with memory and the inability to focus. The patient reported a long history of self-punishing behaviors, especially hitting himself with fists. The patient reported that this aggression toward himself is primarily for relief of anxiety, tension, and frustration.
The patient’s past psychiatric history is positive for depression since 1997, which had been followed in an outpatient clinic for medication management and psychotherapy. The patient had tried different medications in the past but with no benefit. His current medications included sertraline, quetiapine, and clonazepam. He reported that sertraline helped with depression and the anxiety in the past but not currently.
The patient denied any manic symptoms, psychotic symptoms, posttraumatic stress disorder (PTSD) symptoms, or any alcohol use or illicit drug use or abuse. The patient was admitted to the inpatient psychiatric unit for stabilization. Due to failed response to numerous treatment modalities, the patient was offered a trial of selegiline transdermal patch, a monoamine oxidase inhibitor (MAOI) during his hospital stay. The patient was counseled on treatment side effects, interactions, and food/drink restrictions. The patient consented to treatment.
Sertraline was tapered off completely, and clonazepam was offered only on an as-needed basis. This was followed by a wash-out period of 10 days. Selegiline transdermal patch was started in a dose of 6 mg every 24 hours for 2 weeks, during which time the patient showed improved mood but with not much anxiety relief. Selegiline transdermal patch was then increased to 9 mg every 24 hours. During the following 12 days, the patient showed markedly reduced anxiety and reduced self-injurious behaviors and no depressive symptoms. The patient tolerated the MAOI well during hospital course; he had no side effects or interactions with food. At discharge, the patient’s medications also included quetiapine and a reduced dose of clonazepam. The patient’s condition at discharge was very stable.
Selegiline Transdermal Patch
Anxiety and depression disorders are highly comorbid and have overlapping symptom presentations, especially in patients with related affective and anxiety disorders.1 This comorbidity not only has consequences on the differential diagnosis of the disorder but affects the severity and course of the illness and its response to treatment.
Before the introduction of the International Classifications of Diseases (ICD), there was no definite overlap category between mood and anxiety syndromes in any official classificatory system. Therefore, ICD-10 introduced such a category, Mixed Anxiety Depressive Disorder (MAD), in which an individual has anxiety and depressive features that are a cause for clinical concern, but neither set of symptoms meets the criteria for independent mood or anxiety disorder.2
In attempting to accommodate this diagnostic overlap, the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) included the category, Mixed Anxiety-Depressive Disorder, in its appendix, indicating the need for additional study, although its clinical utility is controversial.1 According to several research articles, this comorbidity leads to poorer prognosis for the patient. In addition, results of multiple studies have indicated that the presence of current comorbidity leads to more psychosocial disability, elevated risk of suicide, as well as worse clinical outcome compared with that of depression alone. Therefore, increased consideration for the coexistence of depression and anxiety may be essential.3
Pfeiffer et al. reported in a study they conducted using VA Databases, that close to half of patients in treatment for depression had either a diagnosed anxiety disorder or were prescribed daytime doses of a common anti-anxiety medication.4 They also found that among depressed veterans, comorbid panic disorder, generalized anxiety disorder (GAD), and anxiety disorder NOS were associated with increased odds of suicide deaths.4 Also prescription of an anti-anxiety medication was found to be a strong predictor of completed suicide than any anxiety disorder diagnosis.4
Tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), nefazodone, venlafaxine XR (extended release), mirtazapine, and MAOIs are medications that have demonstrated effectiveness in depression and anxiety.5 Etiologically, it has been postulated that MAOIs inhibit monoamine oxidase (MAO) enzymes from breaking down the monoamines dopamine, norepinephrine, and serotonin neurotransmitters in the central nervous system. These same neurotransmitters are believed to be associated with the genesis and management of mood and anxiety disorders.2
In addition to being effective in depressive disorders, MAOIs have been shown to be effective in controlled studies of patient with panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety and depression, bulimia, PTSD, and borderline personality disorder.6 It may be possible that medications that are principally used as antidepressants (eg, tricyclic antidepressants, MAOIs, and SSRIs) may be as efficacious as anxiolytics,7 although further research is warranted.
Owing to MAOI’s superior efficacy in treating depression, continued efforts have been made to develop more selective and reversible monoamine oxidase inhibitors.8 The selegiline transdermal patch system was approved by the U.S. Food and Drug Administration (FDA) in 2006 for the treatment of depression.9
Selegiline is a MAOI and a dopamine reuptake inhibitor.7 At lower doses (5 to 10 mg), selegiline requires no dietary restrictions and selectively and irreversibly inhibits MAO-B.8,9 Medications that inhibit only MAO-B do not affect gastrointestinal absorption of vasopressors.9 However, at higher daily oral doses, selegiline doses inhibit the enzyme MAO-A, which predominantly metabolizes norepinephrine and serotonin in the gastrointestinal tract, therefore interfering with the body’s ability to regulate the absorption of tyramine and other vasopressors.
At its lowest strength (6 mg/24 hrs), transdermal selegiline offers safe and effective treatment without requiring the dietary restrictions associated with oral MAOIs. However, the higher selegiline patch dosages (9 mg/24 hrs, 12 mg/24 hrs) carry dietary restrictions.10 Although they may lack relevance unless the patient has a diet very rich in tyramine or vasopressors.11
This process consequently increases the potential risk of cardiovascular crises (eg, stroke) associated with a diet rich in vasopressors, including aged cheeses, beef and chicken liver, chocolate, dried sausages, fava beans, Italian green beans, and smoked fish, as well as beer and red and sparkling wines.9–11
Selegiline had been available for many years as a treatment for Parkinson’s disease, but administering it as a patch and to patients with depression is a newer indication.9 Transdermal selegiline delivers the MAOI, selegiline, through the skin into the bloodstream, therefore bypassing metabolism in the gastrointestinal tract and liver, permitting higher plasma levels in the brain, thereby producing anti-depressant effects without inhibiting gastrointestinal MAO-A.9,11
Because comorbid anxiety is strongly associated with the development of chronicity in depression and treatment resistance, psychotherapy might have an especially important adjunctive role in managing patients with these comorbidities.12
The spectrum of comorbid depression and anxiety disorders presents a treatment challenge. The side-effect profile of MAOI limited their use for this condition. Trans-dermal selegiline offers another pharmacologic approach with fewer side effects. However, further clinical research is needed to determine if monotherapy with MAOI is as beneficial as an adjunctive therapy with anxiolytics for comorbid anxiety.
- Dunlop BW, Davis PG. Combination treatment with benzodiazepines and SSRIs for comorbid anxiety and depression: a review. Prim Care Companion J Clin Psychiatry. 2008;10(3):222–228. doi:10.4088/PCC.v10n0307 [CrossRef]
- Aggarwal M, Basu D. Mood disorder and anxiety disorder: How much is the overlap? And what are the implications?Journal of Mental Health and Human Behavior. 2007;12:59–69.
- Mergl R, Seidscheck I, Allgaier AK, Moller HJ, Hergerl U, Henkel V. Depressive, anxiety, and somatoform disorders in primary care: prevalence and recognition. Depress Anxiety. 2007;24(3):185–195. doi:10.1002/da.20192 [CrossRef]
- Pfeiffer PN, Ganoczy D, Ilgen M, Zivin K, Valenstein M. Comorbid anxiety as a suicide risk factor among depressed veterans. Depress Anxiety. 2009;26(8):752–757. doi:10.1002/da.20583 [CrossRef]
- Pollack MH, Marzol PC. Pharmacotherapeutic options in the treatment of comorbid depression and anxiety. CNS Spectr. 2000;5(12):23–30.
- Liebowitz MR, Hollander E, Scheneier F, et al. Reversible and irreversible monamine oxidase inhibitors in other psychiatric disorders. Acta Psychiatr Scand Suppl. 1990;360:29–34. doi:10.1111/j.1600-0447.1990.tb05321.x [CrossRef]
- Levine J, Cole DP, Chengappa KN, Gershon S. Anxiety disorders and major depression, together or apart. Depress Anxiety. 2001;14(2):94–104. doi:10.1002/da.1051 [CrossRef]
- Nandagopal JJ, Delbello MP. Selegiline transdermal system: a novel treatment option for major depressive disorder. Expert Opin Pharmacothey. 2009;10(10):1665–1673. doi:10.1517/14656560903048942 [CrossRef]
- Gorman JM. Leading the way: advances in the diagnosis, treatment, and management of neuropsychiatric illnesses. CNS Spectr. 2006;11(5):338–339.
- Lee KC, Chen JJ. Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2007;3(5):527–537.
- Howland RH. Transdermal selegiline: a novel MAOI formulation for depression. J Psychosoc Nurs Ment Health Serv. 2006;44(7):9–12.
- Howland RH, Thase ME. Comorbid depression and anxiety: when and how to treat. J Psychiatry. 2005;11:891–1047.