# 2004 Taylor & Francis
International Journal of Psychiatry in Clinical Practice
2004 Volume 8 (Suppl 1)
Pages 31 /35
31
Anxiety disorders: does one treatment fit all? DAVID BALDWIN
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/02/14 For personal use only.
University of Southampton, School of Medicine, Southampton, UK
Correspondence Address David Baldwin, University of Southampton, School of Medicine, Southampton, UK Tel: /(44) 23 80 59 44 08 or 23 80 82 55 61 Fax: /(44) 23 80 23 42 43 E-mail: [email protected]
Anxiety disorders are relatively common; almost 30% of the population suffer from some form of anxiety disorder at some point during their life. Anxiety and depressive symptoms often co-exist, and for physicians in primary care the boundaries between depression and anxiety disorders (e.g. generalised anxiety disorder [GAD], social anxiety disorder [SAD], and panic disorder) are often fairly fluid. Differences in treatment tend to occur in patients diagnosed with a pure anxiety disorder and those with comorbid anxiety and depression. For example, the proportion of patients with pure GAD who seek help and get treated for anxiety is much lower than those patients with GAD and comorbid depression. The selective serotonin reuptake inhibitor (SSRI) escitalopram is effective in panic disorder, reducing panic attack frequency and anticipatory anxiety compared with placebo. Furthermore, escitalopram has shown efficacy in patients with SAD and GAD. Antidepressants have potential in treating anxiety disorders, and further novel drug treatments and development of treatment guidelines will be required to effectively manage those patients. (Int J Psych Clin Pract 2004; 8 (Suppl 1): 31 35) /
Keywords anxiety disorders SAD escitalopram
INTRODUCTION
T
he 1990s were labelled the ‘decade of the brain’; awareness of depression and its symptoms were increasingly recognised, understood and treated appropriately. Today, anxiety disorders are recognised as common and burdensome psychiatric conditions in the community and healthcare settings. There are conflicting concerns regarding the treatment of anxiety disorders: is anxiety being diagnosed correctly, is it undertreated and are psychotropic agents over used? New drugs are being developed as potential new approaches in the treatment of anxiety disorders. Furthermore, treatment guidelines are currently being developed to ensure that after a correct diagnosis of anxiety, the patient receives an appropriate and efficacious treatment.
PREVALENCE OF ANXIETY DISORDERS AND COMORBIDITY Several surveys have demonstrated that anxiety is a relatively common disorder. The National Comorbidity Survey
depressive disorders GAD SSRI
(NCS) reported that the 12-month prevalence of anxiety disorders (including panic disorder, generalised anxiety disorder [GAD], agoraphobia without panic, post-traumatic stress disorder, simple phobia and social anxiety disorder [SAD]) is almost 20%, while lifetime prevalence is nearly 30%.1 Substantial comorbidity of anxiety and depressive disorders in primary care was reported by the WHO, who showed that the proportion of patients currently showing anxiety and depressive symptoms was similar (5.6 and 7.1%, for anxiety and depression, respectively) (Figure 1).2 Furthermore, the prevalence for the two disorders existing together was a further 4.6%. Researchers for The Hampshire Depression Project interviewed more than 21 000 patients in primary care with the Hospital Anxiety and Depression (HAD) scale.3 Approximately 20% of the patients were classified as having depression. When anxiety symptoms were assessed, half the patients displayed symptoms (including probable and doubtful cases) (unpublished data, Hampshire Depression Project). These data suggest that anxiety symptoms are more common than depressive symptoms in primary care. DOI: 10.1080/13651500410005531
32
D Baldwin
More recently, the United Kingdom Psychiatric Morbidity Survey reported a higher healthcare use in SAD patients compared with a psychiatrically well population (see Table 1 for summary).7
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/02/14 For personal use only.
USE OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) IN ANXIETY DISORDERS
Figure 1 Comorbidity of ICD-10 anxiety and depressive disorders in primary care. 2
HOW WELL ARE ANXIETY DISORDERS MANAGED? GENERALISED ANXIETY DISORDER Analysis of healthcare use among patients with pure GAD and comorbid GAD using data from the NCS showed that about 70% of patients with comorbid GAD sought professional help compared with 50% of sufferers with pure GAD.4 Psychiatric care was sought by only 18% of patients with pure GAD, which increased to 30% of comorbid patients. Approximately 25 and 45% of patients with pure GAD and comorbid GAD, respectively, were receiving medication. It is unknown, however, if the medication prescribed was appropriate; for example, was the correct dose administered and was the agent suitable for the individual’s symptoms?
SOCIAL ANXIETY DISORDER Healthcare use in patients suffering from SAD has been reported in a number of surveys. The Duke Epidemiological Catchment Area (ECA) study reported that of patients categorised with psychological complaints, about one-third would seek professional help compared with just 3% of patients suffering symptoms of SAD.5 In addition, the NCS demonstrated that fewer patients with SAD sought help (19 vs 41%) or used medication (6 vs 22%) compared with patients with agoraphobia.6
The antidepressant SSRIs have well-documented efficacy in anxiety disorders.8 Escitalopram, the most selective SSRI, has proven efficacy in the treatment of depression.9 12 The efficacy of escitalopram in three anxiety disorders (panic disorder, SAD and GAD) has also been investigated.
ESCITALOPRAM IN ANXIETY DISORDERS PANIC DISORDER The efficacy of escitalopram was investigated in panic disorder, using the Bandelow panic and agoraphobia (P&A) scale.13 Escitalopram showed a continual decline in symptom score from the onset of treatment (Figure 2). Furthermore, significantly superior efficacy compared with placebo was demonstrated from week 4 of treatment. Patients receiving escitalopram experienced a statistically significant reduction (P B/0.05) in panic attack frequency compared with placebo-treated patients. In addition, the reduction in duration of anticipatory anxiety (percentage of time spent) was greater for escitalopram compared with placebo (P 5/0.05). The proportion of patients with zero panic attacks at study endpoint (derived from the P&A scale) was 50 and 38% for the escitalopram and placebo groups, respectively (P /0.051).
SOCIAL ANXIETY DISORDER In a flexible-dose, 10-week study, the efficacy of escitalopram (10 /20 mg/day) compared with placebo in the treatment of SAD was investigated.14
Table 1 Summary of healthcare and medication use in patients with social anxiety disorder (SAD) compared with the control (psychiatrically well) population7
Patients visiting general practitioner in the past year (%) Patients taking CNS medication (%) Patients taking antidepressant treatment (%)
Patients with SAD
Psychiatrically well population (control)
SAD vs control (P value)
27 18 9
14 6.1 0.2
P B/0.01 P B/0.0001 P B/0.0001
P values compare proportion of patients with SAD with proportion of control population.
Anxiety disorders: does one treatment fit all?
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/02/14 For personal use only.
. . . . .
Figure 2 Mean changes from baseline in panic and agoraphobia (P&A) score, by visit, following treatment with placebo or escitalopram (10 /20 mg) adapted from Ref. 13. Note: changes in scores following treatment with escitalopram were statistically different from placebo: *P5/0.05 and **P B/ 0.01.
The decrease in total Liebowitz Social Anxiety Scale (LSAS) score from baseline (primary endpoint) with escitalopram was statistically greater than with placebo (P B/0.01; Figure 3). Furthermore, when the avoidance and fear/anxiety items from the LSAS were analysed separately, escitalopram showed superior efficacy over placebo. A statistically higher response rate (defined as Clinical Global Impression-Improvement [CGI-I] 5/2) was achieved by escitalopram-treated patients than those receiving placebo (P B/0.01). The efficacy of escitalopram has also been compared with that of paroxetine,15 a frequently used treatment in SAD. In a 24-week study, SAD patients were randomised to receive one of the following treatments:
Figure 3 Change from baseline in Liebowitz Social Anxiety Scale (LSAS) score, to end of treatment with escitalopram (10 /20 mg/day) and placebo. Note: reductions in score significantly greater for escitalopram than placebo: *P B/0.05, **P B/0.01 and ***P B/0.001 .14
33
escitalopram, 5 mg/day escitalopram, 10 mg/day escitalopram, 20 mg/day paroxetine, 20 mg/day placebo
The change in LSAS score was the primary efficacy measure. After 24 weeks’ treatment, patients receiving escitalopram (20 mg/day) showed the highest improvement in LSAS score.15 This achievement was significantly greater than that seen for placebo (P B/0.001) and for paroxetine (P B/0.01) (Figure 4). Relapse prevention studies in SAD are useful in determining the long-term efficacy of an active compound. Montgomery et al16 examined the long-term efficacy of escitalopram by adopting a placebo-controlled relapse prevention design. Patients received open-label, flexible doses of escitalopram (10 /20 mg/day) for 12 weeks. Responders (defined as patients with a CGI-scale score of 1 or 2), were randomly assigned to receive double-blind placebo, or to continue on the escitalopram dose to which they responded in the first phase of the trial, for 24 weeks. The time to relapse (defined as an increase in LSAS score of ]/10, from start of double-blind treatment, or loss of efficacy as judged by the investigator) was significantly longer for the patients receiving escitalopram compared with those receiving placebo (P B/0.001). By the end of the 24-week treatment period, almost twice as many patients remained well in the escitalopram group (77%) compared with the placebo group (45%).
GENERALISED ANXIETY DISORDER The efficacy of escitalopram in GAD has also been investigated. In a flexible-dose, 8-week, placebo-controlled trial, GAD patients were randomly allocated to receive escitalo-
Figure 4 Change from baseline in Liebowitz Social Anxiety Scale (LSAS) scores, to end of treatment with paroxetine (PAR), escitalopram (ESC) and placebo. Note: reductions in score significantly greater for escitalopram than placebo: *PB/0.05, **P B/0.01 and ***P B/0.001. //Reduction in score for escitalopram (20 mg/day) significantly greater than for paroxetine 20 mg/ day (PB/0.01) .15
34
D Baldwin
score of 1 or 2) was significantly higher with escitalopram versus placebo (P B/0.01).
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/02/14 For personal use only.
SUMMARY
Figure 5 Mean change from baseline in Hamilton Anxiety Scale (HAM-A) score in patients with generalised anxiety disorder (GAD) following treatment with escitalopram and placebo. 18 Note: reductions in score significantly greater for escitalopram than placebo: *PB/0.05 and **PB/0.01.
Epidemiological studies have indicated that patients with panic disorder, SAD and GAD are frequently undertreated, and that physicians are not always fully aware of the medications available for the successful treatment of these disorders. Escitalopram has proven efficacy in each of these disorders. Separation from placebo has been shown as early as week 1 in studies involving patients with GAD. In the treatment of SAD, superior efficacy with escitalopram has been demonstrated against paroxetine, one of the standard treatments.
KEY POINTS
pram or placebo. The primary endpoint was the change from baseline in total Hamilton Anxiety Scale (HAM-A) score at the end of the trial. Patients treated with escitalopram (10 / 20 mg/day) showed a greater reduction in total HAM-A score compared with those receiving placebo (P B/0.01; Figure 5).17,18 Furthermore, a clear separation of the two groups was apparent as early as week 1 (Figure 5). In addition to a superior reduction in HAM-A score with escitalopram, the number of responders (defined as CGI-I
. Anxiety and depressive symptoms often co-exist . Patients with panic disorder, SAD and GAD are often undertreated, and physicians are not always aware of the effective medications available . Escitalopram has proven efficacy in anxiety disorders against placebo and reference SSRIs such as paroxetine
REFERENCES 1.
2.
3.
4.
5.
6.
7.
Kessler RC, McGonagle KA, Zhao S et al (1994) Lifetime and 12month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51: 8 /19. Sartorius N, .U¨stu¨n B, Lecrubier Y, Wittchen H-U (1996) Depression comorbid with anxiety: results from the WHO study on psychological disorders in primary health care. Br J Psychiatry 168: 38 /43. Thompson C, Kinmonth AL, Stevens L et al (2000) Effects of a clinical-practice guideline and practice-based education on detection and outcome of depression in primary care: Hampshire Depression Project randomised controlled trial. Lancet 355: 185 /91. Wittchen HU, Zhaos S, Kessler RC, Eaton WW (1994) DSM-III-R generalised anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry 51: 355 /64. Davidson JR, Hughes DL, George LK, Blazer DG (1993) The epidemiology of social phobia: findings from the Duke Epidemiological Catchment Area Study. Psychol Med 23: 709 /18. Magee WJ, Eaton WW, Wittchen HU et al (1996) Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry 53: 159 /68. Patel A, Knapp M, Henderson J, Baldwin D (2002) The economic consequences of social phobia. J Affect Disord 68: 221 /33.
8. 9.
10.
11.
12.
13.
14.
15.
Issac M (1999) Where are we going with SSRIs? Eur Neuropsychopharmacol 9 (Suppl 3): S101 /6. Montgomery SA, Loft H, Sa´nchez C et al (2001) Escitalopram (Senantiomer of citalopram): clinical efficacy and onset of action predicted from a rat model. Pharmacol Toxicol 88: 282 /6. Burke WJ, Gergel I, Bose A (2002) Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry 63: 331 /6. Wade AG, Lemming O, Hedegaard K (2002) Escitalopram 10 mg/ day is effective and well-tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol 17: 95 /102. Lepola UM, Loft H, Reines EH (2003) Escitalopram (10 /20 mg/ day) is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol 18: 211 /7. Stahl S, Gergel I, Li D (2003) Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 64: 1322 /7. Kasper S, Loft H, Nil R (2002) Escitalopram is efficacious and well tolerated in the treatment of social anxiety disorder. Nordic J Psych 56: 108. Lader M, Stender K, Bu¨rger V, Nil R (2004) The efficacy and tolerability of escitalopram in the short- and long-term treatment of social anxiety disorder: a randomised, double-blind, placebocontrolled, fixed-dose study. Depr Anxiety 19: 241 /8.
Anxiety disorders: does one treatment fit all?
16.
17.
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/02/14 For personal use only.
18.
Montgomery SA, Du¨rr-Pal N, Loft H, Nil R (2003) Relapse prevention by escitalopram treatment of patients with social anxiety disorder (SAD). Eur Neuropsychopharmacol 13 (Suppl 4): S364. Davidson J, Bose A, Su G (2002) Escitalopram in the treatment of generalized anxiety disorder. Int J Neuropsychopharmacol 5 (Suppl 1): S214. Davidson JRT, Bose A, Korotzer A, Zheng H (2004) Escitalopram in the treatment of generalized anxiety disorder: a double-blind, placebo controlled, flexible dose study. Depr Anxiety 19: 234 /40.
35
FINANCIAL DISCLOSURE Institutional and corporate affiliations: Dr Baldwin’s department has received research grants from: Eli Lilly Ltd., GlaxoSmithKline, Lundbeck Ltd., Pfizer Ltd. and Wyeth Ltd. Dr Baldwin currently attends advisory boards for Eli Lilly Ltd., Lundbeck Ltd. and Hoffman LaRoche.
International Journal of Psychiatry in Clinical Practice
2004 Volume 8 (Suppl 1)
Pages 31 /35
31
Anxiety disorders: does one treatment fit all? DAVID BALDWIN
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/02/14 For personal use only.
University of Southampton, School of Medicine, Southampton, UK
Correspondence Address David Baldwin, University of Southampton, School of Medicine, Southampton, UK Tel: /(44) 23 80 59 44 08 or 23 80 82 55 61 Fax: /(44) 23 80 23 42 43 E-mail: [email protected]
Anxiety disorders are relatively common; almost 30% of the population suffer from some form of anxiety disorder at some point during their life. Anxiety and depressive symptoms often co-exist, and for physicians in primary care the boundaries between depression and anxiety disorders (e.g. generalised anxiety disorder [GAD], social anxiety disorder [SAD], and panic disorder) are often fairly fluid. Differences in treatment tend to occur in patients diagnosed with a pure anxiety disorder and those with comorbid anxiety and depression. For example, the proportion of patients with pure GAD who seek help and get treated for anxiety is much lower than those patients with GAD and comorbid depression. The selective serotonin reuptake inhibitor (SSRI) escitalopram is effective in panic disorder, reducing panic attack frequency and anticipatory anxiety compared with placebo. Furthermore, escitalopram has shown efficacy in patients with SAD and GAD. Antidepressants have potential in treating anxiety disorders, and further novel drug treatments and development of treatment guidelines will be required to effectively manage those patients. (Int J Psych Clin Pract 2004; 8 (Suppl 1): 31 35) /
Keywords anxiety disorders SAD escitalopram
INTRODUCTION
T
he 1990s were labelled the ‘decade of the brain’; awareness of depression and its symptoms were increasingly recognised, understood and treated appropriately. Today, anxiety disorders are recognised as common and burdensome psychiatric conditions in the community and healthcare settings. There are conflicting concerns regarding the treatment of anxiety disorders: is anxiety being diagnosed correctly, is it undertreated and are psychotropic agents over used? New drugs are being developed as potential new approaches in the treatment of anxiety disorders. Furthermore, treatment guidelines are currently being developed to ensure that after a correct diagnosis of anxiety, the patient receives an appropriate and efficacious treatment.
PREVALENCE OF ANXIETY DISORDERS AND COMORBIDITY Several surveys have demonstrated that anxiety is a relatively common disorder. The National Comorbidity Survey
depressive disorders GAD SSRI
(NCS) reported that the 12-month prevalence of anxiety disorders (including panic disorder, generalised anxiety disorder [GAD], agoraphobia without panic, post-traumatic stress disorder, simple phobia and social anxiety disorder [SAD]) is almost 20%, while lifetime prevalence is nearly 30%.1 Substantial comorbidity of anxiety and depressive disorders in primary care was reported by the WHO, who showed that the proportion of patients currently showing anxiety and depressive symptoms was similar (5.6 and 7.1%, for anxiety and depression, respectively) (Figure 1).2 Furthermore, the prevalence for the two disorders existing together was a further 4.6%. Researchers for The Hampshire Depression Project interviewed more than 21 000 patients in primary care with the Hospital Anxiety and Depression (HAD) scale.3 Approximately 20% of the patients were classified as having depression. When anxiety symptoms were assessed, half the patients displayed symptoms (including probable and doubtful cases) (unpublished data, Hampshire Depression Project). These data suggest that anxiety symptoms are more common than depressive symptoms in primary care. DOI: 10.1080/13651500410005531
32
D Baldwin
More recently, the United Kingdom Psychiatric Morbidity Survey reported a higher healthcare use in SAD patients compared with a psychiatrically well population (see Table 1 for summary).7
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/02/14 For personal use only.
USE OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) IN ANXIETY DISORDERS
Figure 1 Comorbidity of ICD-10 anxiety and depressive disorders in primary care. 2
HOW WELL ARE ANXIETY DISORDERS MANAGED? GENERALISED ANXIETY DISORDER Analysis of healthcare use among patients with pure GAD and comorbid GAD using data from the NCS showed that about 70% of patients with comorbid GAD sought professional help compared with 50% of sufferers with pure GAD.4 Psychiatric care was sought by only 18% of patients with pure GAD, which increased to 30% of comorbid patients. Approximately 25 and 45% of patients with pure GAD and comorbid GAD, respectively, were receiving medication. It is unknown, however, if the medication prescribed was appropriate; for example, was the correct dose administered and was the agent suitable for the individual’s symptoms?
SOCIAL ANXIETY DISORDER Healthcare use in patients suffering from SAD has been reported in a number of surveys. The Duke Epidemiological Catchment Area (ECA) study reported that of patients categorised with psychological complaints, about one-third would seek professional help compared with just 3% of patients suffering symptoms of SAD.5 In addition, the NCS demonstrated that fewer patients with SAD sought help (19 vs 41%) or used medication (6 vs 22%) compared with patients with agoraphobia.6
The antidepressant SSRIs have well-documented efficacy in anxiety disorders.8 Escitalopram, the most selective SSRI, has proven efficacy in the treatment of depression.9 12 The efficacy of escitalopram in three anxiety disorders (panic disorder, SAD and GAD) has also been investigated.
ESCITALOPRAM IN ANXIETY DISORDERS PANIC DISORDER The efficacy of escitalopram was investigated in panic disorder, using the Bandelow panic and agoraphobia (P&A) scale.13 Escitalopram showed a continual decline in symptom score from the onset of treatment (Figure 2). Furthermore, significantly superior efficacy compared with placebo was demonstrated from week 4 of treatment. Patients receiving escitalopram experienced a statistically significant reduction (P B/0.05) in panic attack frequency compared with placebo-treated patients. In addition, the reduction in duration of anticipatory anxiety (percentage of time spent) was greater for escitalopram compared with placebo (P 5/0.05). The proportion of patients with zero panic attacks at study endpoint (derived from the P&A scale) was 50 and 38% for the escitalopram and placebo groups, respectively (P /0.051).
SOCIAL ANXIETY DISORDER In a flexible-dose, 10-week study, the efficacy of escitalopram (10 /20 mg/day) compared with placebo in the treatment of SAD was investigated.14
Table 1 Summary of healthcare and medication use in patients with social anxiety disorder (SAD) compared with the control (psychiatrically well) population7
Patients visiting general practitioner in the past year (%) Patients taking CNS medication (%) Patients taking antidepressant treatment (%)
Patients with SAD
Psychiatrically well population (control)
SAD vs control (P value)
27 18 9
14 6.1 0.2
P B/0.01 P B/0.0001 P B/0.0001
P values compare proportion of patients with SAD with proportion of control population.
Anxiety disorders: does one treatment fit all?
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/02/14 For personal use only.
. . . . .
Figure 2 Mean changes from baseline in panic and agoraphobia (P&A) score, by visit, following treatment with placebo or escitalopram (10 /20 mg) adapted from Ref. 13. Note: changes in scores following treatment with escitalopram were statistically different from placebo: *P5/0.05 and **P B/ 0.01.
The decrease in total Liebowitz Social Anxiety Scale (LSAS) score from baseline (primary endpoint) with escitalopram was statistically greater than with placebo (P B/0.01; Figure 3). Furthermore, when the avoidance and fear/anxiety items from the LSAS were analysed separately, escitalopram showed superior efficacy over placebo. A statistically higher response rate (defined as Clinical Global Impression-Improvement [CGI-I] 5/2) was achieved by escitalopram-treated patients than those receiving placebo (P B/0.01). The efficacy of escitalopram has also been compared with that of paroxetine,15 a frequently used treatment in SAD. In a 24-week study, SAD patients were randomised to receive one of the following treatments:
Figure 3 Change from baseline in Liebowitz Social Anxiety Scale (LSAS) score, to end of treatment with escitalopram (10 /20 mg/day) and placebo. Note: reductions in score significantly greater for escitalopram than placebo: *P B/0.05, **P B/0.01 and ***P B/0.001 .14
33
escitalopram, 5 mg/day escitalopram, 10 mg/day escitalopram, 20 mg/day paroxetine, 20 mg/day placebo
The change in LSAS score was the primary efficacy measure. After 24 weeks’ treatment, patients receiving escitalopram (20 mg/day) showed the highest improvement in LSAS score.15 This achievement was significantly greater than that seen for placebo (P B/0.001) and for paroxetine (P B/0.01) (Figure 4). Relapse prevention studies in SAD are useful in determining the long-term efficacy of an active compound. Montgomery et al16 examined the long-term efficacy of escitalopram by adopting a placebo-controlled relapse prevention design. Patients received open-label, flexible doses of escitalopram (10 /20 mg/day) for 12 weeks. Responders (defined as patients with a CGI-scale score of 1 or 2), were randomly assigned to receive double-blind placebo, or to continue on the escitalopram dose to which they responded in the first phase of the trial, for 24 weeks. The time to relapse (defined as an increase in LSAS score of ]/10, from start of double-blind treatment, or loss of efficacy as judged by the investigator) was significantly longer for the patients receiving escitalopram compared with those receiving placebo (P B/0.001). By the end of the 24-week treatment period, almost twice as many patients remained well in the escitalopram group (77%) compared with the placebo group (45%).
GENERALISED ANXIETY DISORDER The efficacy of escitalopram in GAD has also been investigated. In a flexible-dose, 8-week, placebo-controlled trial, GAD patients were randomly allocated to receive escitalo-
Figure 4 Change from baseline in Liebowitz Social Anxiety Scale (LSAS) scores, to end of treatment with paroxetine (PAR), escitalopram (ESC) and placebo. Note: reductions in score significantly greater for escitalopram than placebo: *PB/0.05, **P B/0.01 and ***P B/0.001. //Reduction in score for escitalopram (20 mg/day) significantly greater than for paroxetine 20 mg/ day (PB/0.01) .15
34
D Baldwin
score of 1 or 2) was significantly higher with escitalopram versus placebo (P B/0.01).
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/02/14 For personal use only.
SUMMARY
Figure 5 Mean change from baseline in Hamilton Anxiety Scale (HAM-A) score in patients with generalised anxiety disorder (GAD) following treatment with escitalopram and placebo. 18 Note: reductions in score significantly greater for escitalopram than placebo: *PB/0.05 and **PB/0.01.
Epidemiological studies have indicated that patients with panic disorder, SAD and GAD are frequently undertreated, and that physicians are not always fully aware of the medications available for the successful treatment of these disorders. Escitalopram has proven efficacy in each of these disorders. Separation from placebo has been shown as early as week 1 in studies involving patients with GAD. In the treatment of SAD, superior efficacy with escitalopram has been demonstrated against paroxetine, one of the standard treatments.
KEY POINTS
pram or placebo. The primary endpoint was the change from baseline in total Hamilton Anxiety Scale (HAM-A) score at the end of the trial. Patients treated with escitalopram (10 / 20 mg/day) showed a greater reduction in total HAM-A score compared with those receiving placebo (P B/0.01; Figure 5).17,18 Furthermore, a clear separation of the two groups was apparent as early as week 1 (Figure 5). In addition to a superior reduction in HAM-A score with escitalopram, the number of responders (defined as CGI-I
. Anxiety and depressive symptoms often co-exist . Patients with panic disorder, SAD and GAD are often undertreated, and physicians are not always aware of the effective medications available . Escitalopram has proven efficacy in anxiety disorders against placebo and reference SSRIs such as paroxetine
REFERENCES 1.
2.
3.
4.
5.
6.
7.
Kessler RC, McGonagle KA, Zhao S et al (1994) Lifetime and 12month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51: 8 /19. Sartorius N, .U¨stu¨n B, Lecrubier Y, Wittchen H-U (1996) Depression comorbid with anxiety: results from the WHO study on psychological disorders in primary health care. Br J Psychiatry 168: 38 /43. Thompson C, Kinmonth AL, Stevens L et al (2000) Effects of a clinical-practice guideline and practice-based education on detection and outcome of depression in primary care: Hampshire Depression Project randomised controlled trial. Lancet 355: 185 /91. Wittchen HU, Zhaos S, Kessler RC, Eaton WW (1994) DSM-III-R generalised anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry 51: 355 /64. Davidson JR, Hughes DL, George LK, Blazer DG (1993) The epidemiology of social phobia: findings from the Duke Epidemiological Catchment Area Study. Psychol Med 23: 709 /18. Magee WJ, Eaton WW, Wittchen HU et al (1996) Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry 53: 159 /68. Patel A, Knapp M, Henderson J, Baldwin D (2002) The economic consequences of social phobia. J Affect Disord 68: 221 /33.
8. 9.
10.
11.
12.
13.
14.
15.
Issac M (1999) Where are we going with SSRIs? Eur Neuropsychopharmacol 9 (Suppl 3): S101 /6. Montgomery SA, Loft H, Sa´nchez C et al (2001) Escitalopram (Senantiomer of citalopram): clinical efficacy and onset of action predicted from a rat model. Pharmacol Toxicol 88: 282 /6. Burke WJ, Gergel I, Bose A (2002) Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry 63: 331 /6. Wade AG, Lemming O, Hedegaard K (2002) Escitalopram 10 mg/ day is effective and well-tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol 17: 95 /102. Lepola UM, Loft H, Reines EH (2003) Escitalopram (10 /20 mg/ day) is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol 18: 211 /7. Stahl S, Gergel I, Li D (2003) Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 64: 1322 /7. Kasper S, Loft H, Nil R (2002) Escitalopram is efficacious and well tolerated in the treatment of social anxiety disorder. Nordic J Psych 56: 108. Lader M, Stender K, Bu¨rger V, Nil R (2004) The efficacy and tolerability of escitalopram in the short- and long-term treatment of social anxiety disorder: a randomised, double-blind, placebocontrolled, fixed-dose study. Depr Anxiety 19: 241 /8.
Anxiety disorders: does one treatment fit all?
16.
17.
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/02/14 For personal use only.
18.
Montgomery SA, Du¨rr-Pal N, Loft H, Nil R (2003) Relapse prevention by escitalopram treatment of patients with social anxiety disorder (SAD). Eur Neuropsychopharmacol 13 (Suppl 4): S364. Davidson J, Bose A, Su G (2002) Escitalopram in the treatment of generalized anxiety disorder. Int J Neuropsychopharmacol 5 (Suppl 1): S214. Davidson JRT, Bose A, Korotzer A, Zheng H (2004) Escitalopram in the treatment of generalized anxiety disorder: a double-blind, placebo controlled, flexible dose study. Depr Anxiety 19: 234 /40.
35
FINANCIAL DISCLOSURE Institutional and corporate affiliations: Dr Baldwin’s department has received research grants from: Eli Lilly Ltd., GlaxoSmithKline, Lundbeck Ltd., Pfizer Ltd. and Wyeth Ltd. Dr Baldwin currently attends advisory boards for Eli Lilly Ltd., Lundbeck Ltd. and Hoffman LaRoche.
