Journal of Affective Disorders 59 (2000) 67–69www.elsevier.com/ locate / jad

Brief report

Sertraline in the treatment of mixed anxiety and depression disorder

a , a b*´ ´ ´ ´ ´Jose Luis Carrasco , Marina Dıaz-Marsa , Jeronimo Saiz-Ruiza ´ ´ ´ ´ ´Department of Psychiatry, Hospital Fundacion Jimenez Dıaz, Universidad Autonoma, Av. Reyes Catolicos, 2, 28040, Madrid, Spain

b ´ ´Department of Psychiatry, Hospital Ramon y Cajal, Universidad de Alcala, Madrid, Spain

Received 12 April 1998; received in revised form 1 July 1999; accepted 2 August 1999

Abstract

Background: Mixed anxiety and depression disorder (MAD) has been recognized in ICD-10 as a diagnostic groupincluding those anxious and depressed patients which do not fit sufficient criteria for any major axis I disorders. MAD isusually treated as a combination of anxiety and depression, although there are data indicating that selective serotoninreuptake inhibitors (SSRIs) might be active on both anxiety and depression. Method: 38 patients diagnosed of MADaccording to ICD-10 criteria were treated with flexible doses of sertraline for 8 weeks. Benzodiazepines were not allowedduring the trial. Efficacy was evaluated with the Clinical Global Impression (CGI) improvement scale and with Hamilton’sdepression and anxiety Scales. Personality scales, including the Cloninger’s TCI and Eysenck’s EPQ, were used to test thepredictive value of personality traits in the response to treatment. Results: Anxiety was reduced by 55% and depression by

´60% in Hamilton scales. At week 8, 29 patients were considered responders (CGI 1 o 2). Two patients discontinued the trial,only one of them due to adverse events. The mean dose of sertraline was 83.4 mg/day. Conclusion: Sertraline showed anexcellent tolerability in patients with mixed anxiety–depression disorder despite high levels of baseline anxiety. Theresponse level was high and similar to that reported for patients with major depression. These results warrant furthercontrolled trials to assess the efficacy of SSRIs in MAD. 2000 Elsevier Science B.V. All rights reserved.

Keywords: Mixed anxiety and depression disorder; Anxiety; Depression; Sertraline; SSRIs; Treatment

1. Introduction Classification of Diseases (ICD-10) (World HealthOrganization, 1992), but not the DSM-IV, provides

The severity and the amount of symptoms of the code for mixed anxiety and depression disorderanxiety and depression are not often sufficient to (MAD) (F 41.2). Some studies from primary carewarrant a diagnosis of an axis I mood disorder or an settings suggest that as many as 30% of anxiety andanxiety disorder. For these patients, the International depression syndromes could be included in the MAD

group (Von Korff et al., 1987). Although the symp-toms are less severe in MAD than in other axis I*Corresponding author. Tel.: 1 34-1-550-4917; fax: 1 34-1-disorders, the social and personal burden could be6342-575.

E-mail address: jlcarrasco@fjd.es (J.L. Carrasco) greater due to its chronic nature and the frequent

0165-0327/00/$ – see front matter 2000 Elsevier Science B.V. All rights reserved.PI I : S0165-0327( 99 )00138-X

68 J.L. Carrasco et al. / Journal of Affective Disorders 59 (2000) 67 –69

association with personality disorders (Zinbarg and response was achieved, with a maximum daily doseBarlow, 1991). allowed at 200 mg/day. No specific anxiolytic drugs

Mixed anxiety and depression disorders are usual- were permitted along the study.ly treated in clinical practice with a combination of Efficacy was assessed by reduction in Hamilton’santidepressants and anxiolytic drugs, mostly benzo- anxiety and depression scales and with the improve-diazepines. However, some reports have indicated ment scale of the clinical global impression (CGI).that antidepressants, particularly imipramine, (Kahn Patients scoring 1 (very much improved) and 2et al., 1987) have an specific action on anxiety. In (much improved) in this scale were consideredaddition, anxious depressions seem to respond to responders.SSRIs as effectively as to tricyclics with sedative Statistical analyses of drug efficacy were based oneffects (Filteau et al., 1995), and a specific role in intention to treat, that is, all patients starting thethe treatment of anxiety disorders, particularly panic study were included in the analysis, even thoughdisorder, has been recently demonstrated for SSRI they did not complete the eight weeks of the study.(Jefferson, 1997). In this line, a previous study For comparisons between responders and non-re-showed fluvoxamine to be efficient in patients with sponders paired t tests were used. Pearson’s correla-anxiety and depression (Laws et al., 1990) but it did tion was used to study the relationship of responsenot excluded patients with major depressive dis- with personality traits. Statistical significance wasorders or specific anxiety disorders. To overcome placed at a level of confidence of 95%.this limitation, the present open trial of sertraline forpatients with a diagnosis of mixed anxiety anddepression disorder excluded patients who met 3. Resultscriteria for typical depressive or anxious disorders.

Thirty six patients completed the eight weeks ofthe study. The mean dose of sertraline in the group

2. Method was 83.4 mg/day. The mean reductions in Hamiltonscales were 55% for anxiety and 60% for depression

Thirty eight outpatients (12 men and 26 women) (Fig. 1). At the end of the study 29 patients (76%)with a diagnosis of mixed anxiety and depression (F showed a score of 1 or 2 on the global improvement41.2) according to ICD-10 criteria were treated with scale (clinician version) and were therefore consid-sertraline for 8 weeks. Based on these diagnostic ered responders. Seven patients (24%) were consid-criteria, the patients showed depressive and anxiety ered non-responders at the eighth week and twosymptoms which could be considered as functionallydisabling but did not meet criteria for major depres-sion, dysthymic disorder, generalized anxiety disor-der, postraumatic stress disorder or any other specificanxiety or mood disorder. For inclusion in the study,all the patients were required to have a score . 12and , 18 in the Hamilton Depression Scale (HDRS)and a score . 15 in the Hamilton Anxiety Scale.

The final assessment was made after eight weeksof treatment, with partial assessments at first, secondand fourth weeks of treatment.

Patients underwent a washout period of two weeksbefore entering the study. In this period, ben-zodiacepines were slowly discontinued if they werebeing used. Sertraline was administered in a flexible-dose schedule, starting at 50 mg/day for the first two Fig. 1. Reduction of Hamilton’s depression and anxiety scalesweeks with increases of 50 mg weekly until effective scores after eight weeks of treatment. * p , 0.01.

J.L. Carrasco et al. / Journal of Affective Disorders 59 (2000) 67 –69 69

Health Organization, 1992). For others, MAD repre-sents only subsyndromical forms of anxiety anddepression disorders presenting together and need noadditional denominations (Zinbarg et al., 1994). Inany case, the results of this study suggest thatsertraline could be effective in the treatment of thosepatients with mixed anxiety and depression. Thecontroversial validity of the MAD nosologic labeland the open and not controlled nature of the trial arethe major limitations for the conclusions of thestudy. Nevertheless, the need for placebo-controlledstudies of SSRI in MAD seems to be warranted.

Fig. 2. Time course of anxious and depressive symptoms duringReferencestreatment.

Filteau, M.J., Baruch, P., Lapierre, Y.D., 1995. SSRI in anxious-patients dropped the study before its conclusion. Oneagitated depression: a post-hoc analysis of 279 patients. Int.

at second week due to intolerable side effects and the Clin. Psychopharmacol. 10, 51–54.other at week three due to lack of efficacy. For data Jefferson, J.W., 1997. Antidepressants in panic disorder. J. Clin.

Psychiatry 58 (2), 20–24.analysis purposes, these two patients were includedKahn, R.J., McNair, D.M., Frankenthaler, L.M., 1987. Tryciclicin the non-responders.

treatment of generalized anxiety disorder Special issue: drugMean scores on the Hamilton scales before treat-treatment of anxiety disorders. J. Affective Disord. 13 (2),

ment were 16.1 for depression and 18.8 for anxiety. 145–151.There were no significant differences between re- Laws, D., Ashford, J.J., Anstee, J.A., 1990. A multicentre double-

blind comparative trial of fluvoxamine versus lorazepam insponders and non-responders in the anxiety andmixed anxiety and depression treated in general practice. Actadepression levels at baseline. No significant differ-Psychiatrica. Scand. 81, 185–189.ences in age or duration of illness between re-

Von Korff, M., Shapiro, S., Burke, J.D., Teitlebaum, M., Skinner,sponders and non-responders were found. E.A., German, P., Turner, R.W., Klein, L., Burns, B., 1987.

During the first week there was a 40% decrease in Anxiety and depression in a primary care clinic: comparison ofDiagnostic Interview Schedule General Health Questionnaireanxiety scales. The decrease in depression scales wasand practitioner assesments. Arch. Gen. Psychiatry 44, 152–20% at week two and 50% at week three, suggesting156.that depression improves later than anxiety (Fig. 2).

World Health Organization. International Classification of Mentaland Behavioral disorders. 10th edition. 1992, Geneva.

Zinbarg, R., Barlow, D.H., 1991. Mixed anxiety–depression: anew diagnostic category. In: Rapee, R.M., Barlow, D.H. (Eds.),4. DiscussionChronic Anxiety: Generalized Anxiety Disorder and MixedAnxiety–Depression, Guilford Press, New York.The validity of the mixed anxiety–depression

Zinbarg, R.E., Barlow, D.H., Liebowitz, M., Street, L., Broadhead,syndrome as a separate entity is controversial. For E. et al., 1994. The DSM-IV field trial for mixed anxiety–some, a MAD nosologic category could be of use to depression. Am. J. Psychiatry 151 (8), 1153–1162.identify affective patients of a distinct nature (World