Psychiatry MMC » anxiety

Decreased Use of Antidepressants in Youth After US Food and Drug Administration Black Box Warning

admin — Sat, 31 Oct 2009 19:27:39 +0000

by Tanvir Singh, MD; Ashwin Prakash, MD; Theodore Rais, MD; and Neeta Kumari, MD, MPH

Dr. Singh is Assistant Professor, Department of Child and Adolescent Psychiatry, University of Toledo Medical Center, Toledo, Ohio; Dr. Prakash is from the Department of Child and Adolescent Psychiatry, University of Toledo Medical Center, Toledo, Ohio; Dr. Rais is Associate Professor, Department of Child and Adolescent Psychiatry, University of Toledo Medical Center, Toledo, Ohio; and Dr. Kumari is from the Department of Public Health, University Toledo Medical Center, Toledo, Ohio.

Psychiatry (Edgemont) 2009;6(10):30–34

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Asthma: Wheezing, Woes, and Worries

admin — Tue, 14 Oct 2008 18:52:22 +0000

by Randy A. Sansone, MD, and Lori A. Sansone, MD

Dr. R. Sansone is a professor in the Departments of Psychiatry and Internal Medicine at Wright State University School of Medicine in Dayton, Ohio, and Director of Psychiatry Education at Kettering Medical Center in Kettering, Ohio; Dr. L. Sansone is a family medicine physician (government service) and Medical Director of the Primary Care Clinic at Wright-Patterson Air Force Base. The views and opinions expressed in this column are those of the authors and do not reflect the official policy or the position of the United States Air Force, Department of Defense, or US government.

Psychiatry (Edgemont) 2008;5(10):48–52

ABSTRACT
We examine the associations between asthma and mood and anxiety disorders and between asthma and trauma in childhood and adulthood. Our findings indicate that there is a higher-than-expected prevalence of mood and anxiety disorders among asthmatics as well as a higher frequency of asthma among the traumatized. There are a number of potential confounds in these data, but we close with a proposed risk model.

INTRODUCTION
For many individuals, asthma is a chronic and potentially life-threatening disease. According to the Centers for Disease Control and Prevention (CDC), the lifetime prevalence of asthma in the US population is approximately 11 percent.[1] However, rates appear to be accelerating. A recent national surveillance report from the CDC indicates that between the years 1980 and 1996, the 12-month prevalence rate of asthmatic disease verifiably increased.[2] Given that approximately 1 in 10 Americans suffers from this sporadic lung dysfunction, we wondered if there were any interfacing clinical facets between asthma and psychiatry. In exploring this, we will first examine the evidence for possible relationships between asthma and mood and anxiety disorders. Then, we will review the available data on the relationships between asthma and psychological trauma, both in childhood and adulthood.

THE PREVALENCE OF MOOD AND ANXIETY DISORDERS IN ASTHMATICS
One approach to exploring a potential clinical interface between asthma and psychiatric phenomena is to examine whether particular Axis I disorders are over-represented in individuals who suffer from the disease. In our review of the literature, both mood and anxiety disorders clearly emerge as the predominant psychiatric syndromes associated with asthmatic disease.

Mood disorders in asthmatics. A number of studies have examined the prevalence of mood disorders among individuals suffering from asthma. For example, Brown, Khan, and Mahadi examined 32 patients with asthma and found that 25 percent evidenced current major depression.[3] Afari and colleagues explored mood disorders among 50 outpatients with asthma and, in comparison with a national probability sample, found higher lifetime rates.[4] Among 317 inner-city patients being treated for asthma, Goethe and colleagues found that 55 percent scored positively for depression.[5] Using data from the World Mental Health Survey, investigators examined 18 population surveys from 17 countries (over 85 thousand individuals) and found that depressive disorders were more frequent among those participants with asthma.[6] In a Dutch sample of older adults, researchers found a statistical association between asthmatic disease and major depression.[7] Finally, in a methodologically well executed German study, Goodwin, Jacobi, and Thefeld found that current asthma (non-severe) was clearly associated with an increased likelihood of an affective disorder (OR, 2.42; 95% CI, 1.03–5.72).[8]

Given the prevalence of mood disorders among individuals with asthma, one might wonder about whether there is a correspondingly higher rate in this population of suicidal ideation and/or suicide attempts. Examining data from the National Comorbidity Survey Replication study, Clarke and colleagues initially determined that 12 percent of the overall sample suffered from asthma.[9] In further analyses, the researchers found a statistically significant association between asthma and suicidal ideation with attempts (ORc, 1.98; 95% CI, 1.42–2.76), but not suicidal ideation without attempts (ORc, 1.09; 95% CI, 0.81–1.45).

Finally, if mood disorders are genuinely over-represented in asthmatic probands, one would wonder about the corresponding rates of mood disorders in family members, as well. Wamboldt and colleagues examined this relationship in a clinical sample of 145 first-degree relatives of asthmatic adolescents, and found a link between asthma and familial affective disorders.[10]

Anxiety disorders in asthmatics. In addition to the studies exploring mood disorders among asthmatics, there are a number of studies that have examined relationships between asthma and various anxiety disorders.

Any anxiety disorder. Among 20 adult patients with brittle asthma, Garden and Ayres found that 35 percent evidenced a lifetime history of some type of anxiety disorder, compared to 15 percent of controls.[11] Bussing, Burket, and Kelleher examined 37 children with asthma and found that, compared with controls, the former had a significantly greater number of anxiety disorders.[12] Goodwin, Jacobi, and Thefeld explored anxiety disorders and their relationships to asthma among a German sample of more than 7,000 individuals.[8] Current severe asthma symptoms were associated with a significantly increased likelihood of any anxiety disorder (OR, 2.65; 95% CI, 1.35–5.18). In an international study, Scott and colleagues found an association between asthma and the presence of any anxiety disorder.[6] Finally, in a study of 82 children and adolescents, Vila and colleagues found that generalized anxiety disorder was the most common diagnosis among their asthmatic population and affected nearly 30 percent of participants.[13]

Panic disorder. In addition to any type of anxiety disorder, a number of studies have examined the prevalence of panic disorder in asthmatic populations. In the general population, the prevalence of panic disorder is 4.7 percent.14 In a study of 93 asthmatics, Carr and colleagues found that 23 percent reported histories of panic attacks.[15] In an Italian sample of adults, Perna and colleagues found higher rates of panic disorder than the rates encountered in the general population.[16] Brown, Khan, and Mahadi found a prevalence rate for panic disorder of 16 percent in their sample of asthmatics.[3] Finally, in a Brazilian sample, Nascimento and colleagues reported a prevalence rate for panic disorder of 14 percent.[17]

Data Confounds
The preceding data indicate that among various community and clinical populations of adolescent and adult patients with asthma, there appears to be a higher-than-expected prevalence rate of mood and anxiety disorders. However, these data must be interpreted with caution. First, in some studies, the diagnosis of asthma was based upon self-report. We do not know if these individuals genuinely suffered from asthma—a factor that could contribute to selection bias. Second, the presence of a chronic medical condition may partially explain the high rates of mood and anxiety disorders. In our experience, mood and anxiety disorders are the most common psychiatric syndromes encountered in chronic disease states. Thus, these psychiatric findings may not be specific to the asthma disease state, itself, but rather to chronicity. Third, the medications used in the treatment of asthma may partially explain the observed psychiatric findings. For example, corticosteroids can contribute to mood disorders; the Food and Drug Administration is currently investigating montelukast with regard to mood and behavioral changes, suicidal ideation, and suicide; and beta agonists may cause nervousness and simulate anxiety syndromes. Finally, family studies among asthmatics suggest a possible genetic predisposition to depression, suggesting that asthma may function as a mediating variable. Any of these preceding factors could diminish a genuinely independent relationship between asthma, and mood and anxiety disorders.

From another perspective, the rates of psychiatric disturbance observed in these populations may actually under-represent the association between asthma and mood/anxiety disorders. Specifically, a number of these studies examined child and adolescent populations and report current prevalence rates. Given an increasing risk for mood and anxiety disorders with age, these studies may under-represent the ultimate findings that one would encounter in adults.

Asthma and Psychological Trauma in Childhood/ Adulthood
Given that mood and anxiety disorders appear to demonstrate a higher-than-expected association with asthmatic disease, is there any evidence that trauma histories are present in the lives of these individuals? If so, it is possible that trauma might function as yet another contributory or priming variable for mood and anxiety disorders. In support of this possibility, Ross and Wong discuss the role of anxiety sensitivity (i.e., one’s potential susceptibility to anxiety symptoms), which they attribute to both genetics and the environment.[18] They describe emotional and physical abuses in childhood as important etiological factors for the subsequent development of anxiety sensitivity, which may act as a contributory variable in the ultimate expression of mood and/or anxiety disorders.

While the literature in this area is relatively sparse, there are several elucidative studies. Most of these studies are based upon a similar methodology—the comparison among traumatized individuals of the actual versus expected frequencies of various medical disorders. For example, in a study of adolescents residing in Hong Kong, investigators surveyed more than 3,300 students regarding their exposure to corporal punishment at home. Corporal punishment, including being beaten for no reason and being beaten to the point of injury, was associated with a higher frequency of particular psychological and physical morbidities including asthma.[19] In a study of 502 primary care patients with anxiety, investigators found a relationship between post-traumatic stress disorder and a number of medical problems including asthma.[20] Among a sample of women residing in New Zealand, investigators found that childhood sexual abuse was related to the presence of current asthma (i.e., the past 12 months) (OR, 2.25; 95% CI, 1.06–4.80).[21] In a sample of Australian Vietnam veterans, O’Toole and Catts found that posttraumatic stress disorder was associated with a variety of illnesses including asthma.[22]

Using a different methodological approach and in keeping with the preceding data, Potoczek and colleagues examined 97 patients with severe asthma for evidence of interpersonal loss.[23] In this sample, 80 percent reported the suffering and/or death of an individual whom they were emotionally close to. Likewise, in a 21-year longitudinal study, investigators explored relationships between asthma and mood and anxiety disorders; importantly, exposure to childhood adversity appeared to be an important mediating variable.[24]

These scant preceding data suggest that, in some individuals, early-developmental and adulthood trauma have associations with asthmatic disease. So, in addition to genetics and medications, trauma may secondarily mediate the emergence of mood and anxiety disorders in patients with existing asthma.

A Risk Model
Like many psychiatric syndromes, a risk model is perhaps the most practical way to integrate these various data. At the outset, genetics (i.e., a positive family history of mood disorders and/or predisposition to anxiety sensitivity) contribute to the development of mood and anxiety disorders in patients with asthma. Then, childhood adversity and the effects of chronic illness may have mediating roles in conjunction with trauma in adulthood and the medications used in the treatment of asthma. This model is illustrated in Figure 1 and does not exclude other mediating or contributory variables.

Conclusion
In summarizing these data, it appears that individuals with asthma have a higher-than-expected rate of comorbid mood and anxiety disorders. In our opinion, this is not an unexpected conclusion given our observation that mood and anxiety disorders appear to be commonly associated with chronic illness. However, there are also higher rates of mood disorders in the families of asthmatic individuals, suggesting a genetic predisposition—perhaps to both asthma and mood disorders. In addition, these prevalence rates may be mediated to some degree by the medications used in the treatment of asthma as well as trauma in either childhood or adulthood. Therefore, when evaluating individuals with asthma, we wish to stress the importance of exploring mood and anxiety disorders with special attention to a family history of mood disorders, a history of trauma in childhood or adulthood, and the potential role of medications. Clearly, this is a cohort of patients who are plagued by wheezing (asthma), woes (mood disorders), and worries (anxiety).

References
1. Lifetime Asthma Prevalence Percents by Age, United States: National Health Interview Survey, 2006. http://www.cdc.gov/asthma/nhis/06/table2-1.htm. Accessed June 2, 2008.
2. US Centers for Disease Control. National Surveillance for Asthma—United States, 1980–2004. http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5608a1.htm Accessed June 2, 2008.
3. Brown ES, Khan DA, Mahadi S. Psychiatric diagnoses in inner city outpatients with moderate to severe asthma. Int J Psychiatry Med. 2000;30:319–327.
4. Afari N, Schmaling KB, Barnhart S, Buchwald D. Psychiatric comorbidity and functional status in adult patients with asthma. J Clin Psychol Med Settings. 2001;8:245–252.
5. Goethe JW, Maljanian R, Wolf S, Hernandez P, Cabrera Y. The impact of depressive symptoms on the functional status of inner-city patients with asthma. Ann Allergy Asthma Immunol. 2001;87:205–210.
6. Scott KM, Von Korff M, Ormel J, et al. Mental disorders among adults with asthma: results from the World Mental Health Survey. Gen Hosp Psychiatry. 2007;29:123–133.
7. Wainwright NWJ, Surtees PG, Wareham NJ, Harrison BDW. Psychosocial factors and asthma in a community sample of older adults. J Psychosom Res. 2007;62:357–361.
8. Goodwin RD, Jacobi F, Thefeld W. Mental disorders and asthma in the community. Arch Gen Psychiatry. 2003;60:1125–1130.
9. Clarke DE, Goodwin RD, Messias ELM, Eaton WW. Asthma and suicidal ideation with and without suicide attempts among adults in the United States: what is the role of cigarette smoking and mental disorders? Ann Allergy Asthma Immunol. 2008;100:439–446.
10. Wamboldt MZ, Weintraub P, Krafchick D, Wamboldt FS. Psychiatric family history in adolescents with severe asthma. J Am Acad Child Adolesc Psychiatry. 1996;35:1042–1049.
11. Garden GM, Ayres JG. Psychiatric and social aspects of brittle asthma. Thorax. 1993;48:501–-505.
12. Bussing R, Burket RC, Kelleher ET. Prevalence of anxiety disorders in a clinic-based sample of pediatric asthma patients. Psychosomatics. 1996;37:108–115.
13. Vila G, Nollet-Clemencon C, de Blic J, Mouren-Simeoni MC, Scheinmann P. Prevalence of DSM IV anxiety and affective disorders in a pediatric population of asthmatic children and adolescents. J Affect Disord. 2000;58:223–231.
14. Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:593–602.
15. Carr RE, Lehrer PM, Rausch LL, Hochron SM. Anxiety sensitivity and panic attacks in an asthmatic population. Behav Res Ther. 1994;32:411–418.
16. Perna G, Bertani A, Politi E, Colombo G, Bellodi L. Asthma and panic attacks. Biol Psychiatry. 1997;42:625–630.
17. Nascimento I, Nardi AE, Valenca AM, et al. Psychiatric disorders in asthmatic outpatients. Psychiatry Res. 2002;110:73–80.
18. Ross EJ, Wong S. News from the 24th annual conference of the Anxiety Disorders Association of America. Prim Psychiatry. 2004;11:13–16.
19. Lau JTF, Liu JLY, Cheung JCK, Yu A, Wong CK. Prevalence and correlates of physical abuse in Hong Kong Chinese adolescents: a population-based approach. Child Abuse Negl. 1999;23:549–557.
20. Weisberg RB, Bruce SE, Machan JT, et al. Nonpsychiatric illness among primary care patients with trauma histories and posttraumatic stress disorder. Psychiatr Serv. 2002;53:848–854.
21. Romans S, Belaise C, Martin J, Morris E, Raffi A. Childhood abuse and later medical disorders in women. Psychother Psychosom. 2002;71:141–150.
22. O’Toole BI, Catts SV. Trauma, PTSD, and physical health: an epidemiological study of Australian Vietnam veterans. J Psychosom Res. 2008;64:33–40.
23. Potoczek A, Nizankowska-Mogilnicka E, Bochenek G, Szczeklik A. Difficult asthma and gender of patients versus the presence of profound psychological trauma. Psychiatria Polska. 2006;40:1081–1096.
24. Goodwin RD, Fergusson DM, Horwood LJ. Asthma and depressive and anxiety disorders among young persons in the community. Psychol Med. 2004;34:1465–1474.

Author AffiliationS:
Address correspondence to:
Randy A. Sansone, MD, Sycamore Primary Care Center, 2115 Leiter Road, Miamisburg, OH 45342; Phone: (937) 384-6850; Fax: (937) 384-6938; E-mail: Randy.sansone@khnetwork.org

Use of Benzodiazepines in the Treatment of Anxiety

admin — Tue, 16 Sep 2008 20:01:44 +0000

by Elisa Cascade and Amir H. Kalali, MD

Ms. Cascade is Vice President, Quintiles Inc./iGuard, Falls Church, Virginia; and Dr. Kalali is Vice President, Global Therapeutic Group Leader CNS, Quintiles Inc., San Diego, California, and Professor of Psychiatry, University of California, San Diego.

Psychiatry (Edgemont) 2008;5(9):21–22

Abstract

We examined the role of benzodiazepines in the treatment of anxiety by both psychiatrists and primary care physicians. Over the past year, 112.8 million prescriptions were filled for a benzodiazepine: 55 percent were prescribed by a primary care physician, 16 percent by a psychiatrist, and the remaining 29 percent of prescriptions by another type of specialty physician. Benzodiazepine monotherapy is much more common in the treatment of anxiety by primary care physicians (42%) than psychiatrists (22%). Even when both benzodiazepine monotherapy and combination regimens are considered, total benzodiazepine use remains slightly greater in primary care than psychiatry (51% vs. 42%).

Key words

anxiety, benzodiazepine, antidepressant, monotherapy, combination therapy, psychiatrist, primary care physician

Introduction

Benzodiazepines remain an important option for treatment of anxiety. In this article, we examine the role of benzodiazepines in the treatment of anxiety by both psychiatrists and primary care physicians.

Methods

We obtained data from the following sources: 1) total benzodiazepine prescriptions from SDI Health’s (formerly Verispan) VONA, July 2007 to June 2008 and 2) July 2007 to June 2008 data from SDI Health’s Prescription Drug and Diagnosis Audit (PDDA) regarding products used to treat anxiety (ICD-9 diagnosis code 300). PDDA captures data on disease state and associated therapy from 3,100 office-based physicians representing 29 specialties across the United States.

Results

Over the past year, 112.8 million prescriptions were filled for a benzodiazepine. Slightly more than half of all benzodiazepine prescriptions (55%) were written by primary care physicians. Psychiatrists accounted for an additional 16 percent of prescriptions, and the remaining 29 percent of prescriptions were written by another type of specialty physician (Figure 1).

Figure 2 displays use of antidepressants and benzodiazepines in the treatment of anxiety by primary care physicians and psychiatrists. As seen in Figure 2, benzodiazepine monotherapy is much more common in the treatment of anxiety by primary care physicians (42%) than psychiatrists (22%). Even when both benzodiazepine monotherapy and combination regimens are considered, total benzodiazepine use remains slightly greater in primary care than psychiatry (51% vs. 42%).

Varying Uses of Anticonvulsant Medications

admin — Wed, 18 Jun 2008 19:37:44 +0000

by Elisa Cascade; Amir H. Kalali, MD; and Richard H. Weisler, MD

Ms. Cascade is Vice President, Quintiles Inc./iGuard, Falls Church, Virginia; Dr. Kalali is Vice President, Global Therapeutic Group Leader CNS, Quintiles Inc., San Diego, California, and Professor of Psychiatry, University of California, San Diego; and Dr. Weisler is an Adjunct Professor of Psychiatry at the University of North Carolina, Chapel Hill and Adjunct Associate Professor of Psychiatry at Duke University, Durham, North Carolina.

Financial Disclosures

Dr. Weisler is or has been a consultant to, on the speakers bureaus of, and/or received research support from the National Institute of Mental Health, Abbott, AstraZeneca, Biovail, Bristol-Myers Squibb, Burroughs Wellcome, Cephalon, Ciba Geigy, CoMentis, Corcept, Eisai, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Johnson & Johnson, Lundbeck, McNeil Pharmaceuticals, Medicinova, Merck, Neurochem, New River Pharmaceuticals, Novartis, Organon, Otsuka America Pharma, Pfizer, Pharmacia, Saegis, Sanofi, Sanofi-Synthelabo, Schwabe/Ingenix, Shire, Solvay, Synaptic, TAP, UCB Pharma, Validus, Vela, and Wyeth; and has been or is a stockholder in Bristol Myers Squibb, Cortex, Merck, and Pfizer.

Abstract

In this article, we identify commonly prescribed anticonvulsant medications and characterize central nervous system (CNS) reasons for use. Primary care physicians prescribe 37 percent of all anticonvulsant medications in the US. Psychiatrists are the second highest prescribers with a 19-percent share, and neurologists account for 16 percent of all anticonvulsant medication prescriptions. The top three agents prescribed by psychiatrists are clonazepam, lamotrigine, and divalproex; neurologists most commonly prescribe topiramate, gabapentin, and levetiracetam. Anticonvulsant medications most commonly prescribed by psychiatrists are primarily used for bipolar disorder and anxiety. In contrast, these indications account for less than 10 percent of uses for the top products commonly prescribed by neurologists.

Key words

anticonvulsant medication, seizure medication, clonazepam, lamotrigine, divalproex, topiramate, gabapentin, levetiracetam, carbamazepine, bipolar disorder, anxiety, epilepsy, migraine, pain
Introduction

Although there are more than 30 medications available today for the treatment of seizures, the profile of these agents and utility in other disease areas vary widely. In this article, we identify commonly prescribed anticonvulsant medications and characterize central nervous system (CNS) reasons
for use.

Methods

We obtained data from two different sources: 1) total retail prescriptions of anticonvulsant medications in 1st Quarter 2008 from Vector One National (VONA), which captures nearly half of all prescription activity in the US; and 2) annual data from Verispan’s Prescription Drug and Diagnosis Audit (PDDA) database regarding reasons for use of each anticonvulsant medication. PDDA captures data on disease states and associated therapies from 3,100 office-based physicians representing 29 specialties across
the US.

Results

As seen in Figure 1, primary care physicians prescribe 37 percent of all anticonvulsant medications in the US. Psychiatrists are the second highest prescribers with 19-percent share, and neurologists account for 16 percent of all anticonvulsant medication prescriptions. The remaining 27.7 percent of anticonvulsant medications are prescribed by a variety of specialties with no one group accounting for more than five percent. The top three agents prescribed by psychiatrists are clonazepam, lamotrigine, divalproex. In contrast, neurologists most commonly use topiramate, gabapentin, and levetiracetam.

Figure 2 contains a breakdown of reasons of use for the top anticonvulsant medications prescribed by psychiatrists and neurologists. As seen in Figure 2, anticonvulsant medications most commonly prescribed by psychiatrists are primarily used for bipolar disorder and anxiety, making up 68 percent of the reasons for use for clonazepam, 69 percent of lamotrigine, and 58 percent of divalproex by psychiatrists. These indications, however, account for less than 10 percent of uses for the top products prescribed by neurologists, which include topiramate, gabapentin, and levetiracetam. Instead, medications commonly prescribed by neurologists are used to treat seizures, migraines, and pain, making up 73 percent of the reasons for use for topiramate, 77 percent of gabapentin, and 92 percent of levetiracetam by neurologists.

Commentary

by Richard H. Weisler, MD

The data presented in this article, as highlighted in Figure 2, clearly reveal that clinicians have embraced some of the uniqueness of each of the included seizure medications.

While all of the seizure medications reported on are effective in helping to control seizures, some, like divalproex and carbamazepine (not included in this article’s data), are also very effective for controlling mania acutely.[1] Divalproex and carbamazepine are probably also effective as maintenance agents in preventing episodes of mania, though this later use has yet to be clearly proven. On the other hand, clinicians generally have realized that lamotrigine is better at treating depressive symptoms in bipolar disorder than divalproex and perhaps carbamazepine, although they each help ameliorate depressive symptoms to some degree. In contrast, divalproex and carbamazepine in numerous trials have been shown to be more effective at treating manic symptoms than lamotrigine, although lamotrigine also helps prevent manic symptoms to some degree as noted in lamotrigine’s FDA approval indication.

The presented data analysis in this article reveal that gabapentin and topiramate are still being used by a relatively small percentage of clinicians to treat bipolar disorder, though the clinical trial data clearly show that neither is effective for treating either mania or depression. Some clinicians perhaps may be taking advantage of topiramate’s ability to decrease both appetite and weight or help with alcohol abuse and dependence, as those conditions are frequently comorbid in bipolar patients. Gabapentin can also help control anxiety and pain symptoms, and perhaps clinicians have taken advantage of gabapentin being an effective treatment for these symptoms in some bipolar patients because of the abuse liability of benzodiazepines, opiates, and other pain medications.[2–4]

Neurologists and some psychiatrists have also taken advantage of pregabalin (not included in this article’s data), another FDA-approved an alpha 2-delta-ligand, to ameliorate pain and anxiety symptoms in a similar fashion. Not surprisingly, pregabalin, like gabapentin, does not appear to be effective in treating either manic or depressive symptoms, though several studies have shown that it is effective in some anxiety disorders. As a very large percentage of bipolar patients are being treated with multiple medications, let’s hope that gabapentin, pregabalin, and topiramate are used only in rare exceptions by clinicians as standalone treatments for bipolar disorder due to their lack of efficacy for mania or depression.

Clonazepam can, in some cases, be used to treat seizures. Far more commonly, clonazepam is used like the other benzodiazepine class members to rapidly and effectively control anxiety symptoms as reflected in the prescribing patterns. Clonazepam’s speed of response makes it a very useful drug in generalized anxiety disorder as well as panic disorder and social phobia.[5] Clonazepam relieves anxiety symptoms rapidly even without chronic dosing, which is consistent with it frequently being used on an as-needed basis by clinicians in these situations. Clonazepam as a monotherapy treatment is clearly not an effective treatment for mania, and it can even exacerbate depression in some cases. This suggests that clonazepam is being used by psychiatrists to control pure or comorbid anxiety symptoms and perhaps as a sleep aide. Clonazepam also carries some abuse risks. Unlike the other seizure medications in this article’s data, abrupt discontinuation of clonazepam, even in patients without epilepsy, can lead to withdrawal seizures after regular use.

Neurologists diagnose and treat many more patients for their epilepsy than psychiatrists and this is reflected in their prescribing patterns.[6,7] Neurologists also treat far more patients for migraines than psychiatrists. Not surprisingly, neurologists use more topiriamate and, to some degree, divalproex for migraine headaches as both compounds have FDA disease indications for migraines.[6] Neurologists have recognized that levitracetam is a very effective and generally well-tolerated anticonvulsant. Trials seem to suggest though that levitracetam is not very effective in treating anxiety or mood disorders. Apparently, clinicians have adopted this view of levitracetam as well with wide usage by neurologists for epilepsy and little use outside of that disease area.[8]

All of the seizure medications in Figure 2 are also being used in a substantial minority of cases for other uses. Fibromyalgia, I am certain, represents one of the “other” common indications for gabapentin and pregabalin.[9] These “other uses” may also reflect the breadth of action for antiepileptics and/or the many still unmet clinical needs that clinicians are attempting to address.

As a class, existing and future seizure medications are likely to continue to be very widely used and to remain attractive compounds both for neurologists and psychiatrists. My personal belief is that many other very exciting uses for seizure medications have yet to be identified. Kanner recently reviewed the evidence for the bidirectional link between depression and epilepsy.[10] And one shouldn’t forget that neurologists and psychiatrists share a common organization for board certification for a reason, though each specialty has their own focus of practice. Unmet clinical need will likely drive this clinical exploration of new uses for antiepileptics. For example, additional and more effective treatments for posttraumatic stress disorder (PTSD),[11,12] affective disorders, and traumatic brain injuries (TBI) are desperately needed at this time. A recent Rand Corporation mental health survey of recently returned troops from Iraq and Afghanistan (N=1,965)[13] estimates that of these 1.64 million war veterans, currently about 300,000 (18.5 %) meet criteria for PTSD or depression, about 320,000 (19.5 %) report experiencing a probable TBI, and 120,000 (7.3 %) report having PTSD or depression and experiencing probable TBI. Will some antiepileptics ultimately turn out to be of help for these soldiers and others with affective, anxiety, and cognitive problems like those who have been injured in motor vehicle accidents or assaults? In 1993, in desperation, I first tried the then unapproved drug lamotrigine under a compassionate use exemption for two very refractory patients based only on my clinical hunch and Robert Post’s anti-kindling theory. My two patients, their families, and I were pleasantly shocked a few short weeks later when lamotrigine dramatically lifted their severe unremitting depression and controlled their mood cycling. In 2003, lamotrigine was approved for bipolar disorder by the FDA.[14] I know there will be more stories of new uses like this one for “seizure medications” in the future.

References
1. Weisler RH, Cutler AJ, Ballenger JC, et al. The use of antiepileptic drugs in bipolar disorders: a review based on evidence from controlled trials. CNS Spectr. 2006;11(10):788–799. Review.
2. Rosenberg JM, Salzman C. Update: new uses for lithium and anticonvulsants. CNS Spectr. 2007;12(11):831–841. Comment in: CNS Spectr. 2008;13(2):109–110; author reply 110.
3. Zwanzger P, Eser D, Rupprecht R. [Anticonvulsants in the treatment of anxiety—an alternative treatment option?] Nervenarzt. 2007;78(11):1274–1282.
4. Van Ameringen M, Mancini C, Pipe B, Bennett M. Antiepileptic drugs in the treatment of anxiety disorders: role in therapy. Drugs. 2004;64(19):2199–2220.
5. Nardi AE, Perna G. Clonazepam in the treatment of psychiatric disorders: an update. Int Clin Psychopharmacol. 2006;21(3):131–142.
6. Wilby J, Kainth A, Hawkins N, et al. Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation. Health Technol Assess. 2005;9(15):1–157, iii–iv.
7. Otoul C, Arrigo C, van Rijckevorsel K, French JA. Meta-analysis and indirect comparisons of levetiracetam with other second-generation antiepileptic drugs in partial epilepsy. Clin Neuropharmacol. 2005;28(2):72–78.
8. Mulleners WM, Chronicle EP. Anticonvulsants in migraine prophylaxis: a Cochrane review. Cephalalgia. 2008;28(6):585–597
9. Goldenberg DL. Pharmacological treatment of fibromyalgia and other chronic musculoskeletal pain. Best Pract Res Clin Rheumatol. 2007;21(3):499–511.
10. Kanner AM. Depression in epilepsy: a complex relation with unexpected consequences. Curr Opin Neurol. 2008;21(2):190–194.
11. Berlin HA. Antiepileptic drugs for the treatment of post-traumatic stress disorder. Curr Psychiatry Rep. 2007;9(4):291–300.
12. Davidson JR. Pharmacologic treatment of acute and chronic stress following trauma: 2006. J Clin Psychiatry. 2006;67 Suppl 2:34–39.
13. Tanielian T, Jaycox LH, (eds). Invisible Wounds of War: Psychological and Cognitive Injuries, Their Consequences, and Services to Assist Recovery. Santa Monica, CA: RAND Corporation, MG-720-CCF, 2008:492.
14. Weisler RH, Calabrese JR, Bowden CL, et al. Discovery and development of lamotrigine for bipolar disorder: a story of serendipity, clinical observations, risk taking, and persistence. J Affect Disord. 2008;108(1-2):1–9. Epub 2007 Nov 14. Review.