Bandelow B, Sher L, Bunevicius R, Hollander E, Kasper S, Zohan J et al. Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract 16: 77-84

Article (PDF Available)inInternational Journal of Psychiatry in Clinical Practice 16(2):77-84 · April 2012with111 Reads
DOI: 10.3109/13651501.2012.667114 · Source: PubMed
Abstract
Anxiety disorders are frequently under-diagnosed conditions in primary care, although they can be managed effectively by general practitioners. This paper is a short and practical summary of the World Federation of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) for the treatment in primary care. The recommendations were developed by a task force of 30 international experts in the field and are based on randomized controlled studies. First-line pharmacological treatments for these disorders are selective serotonin reuptake inhibitors (for all disorders), serotonin-norepinephrine reuptake inhibitors (for some) and pregabalin (for generalized anxiety disorder only). A combination of medication and cognitive behavior/exposure therapy was shown to be a clinically desired treatment strategy. This short version of an evidence-based guideline may improve treatment of anxiety disorders, OCD, and PTSD in primary care.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
a
Chair: Robertas Bunevicius (Lithuania), Co-Chair: Siegfried Kasper (Austria), Secretary: Florence Thibaut (France), Members: Wioletta Baranska-Rybak
(Poland), Wieclaw J. Cubala (Poland), David Fiellin (USA), Henry R. Kranzler (USA), Alison Moore (USA), Elmars Rankans (Latvia), Jill Rasmussen (UK),
Richard Saitz (USA), Djea Saravane (France), Thomas E. Schlaepfer (Germany), Leo Sher (USA), S.W. Tang (Hong Kong), Leonas Valius (Lithuania), David
Wong (Hong Kong), Larisa M Zhitnikova (Russia), Joseph Zohar (Israel).
b
Chair: Joseph Zohar (Israel); Co-Chairs: Eric Hollander (USA), Siegfried Kasper (Austria), Hans-Jurgen Moller (Germany); Secretary: Borwin Bandelow
(Germany); Members: C. Allgulander, J. Ayuso-Gutierrez, D. Baldwin, R. Bunevicius, G. Cassano, N. Fineberg, L. Gabriels, I. Hindmarch, H. Kaiya, D.F.
Klein, M. Lader, Y. Lecrubier, J.P. Lepine, M.R. Liebowitz, J.J. Lopez-Ibor, D. Marazitti, E.C. Miguel, K.S. Oh, M. Preter, R. Rupprecht, M. Sato, V. Starcevic,
D.J. Stein, M. van Ameringen, J. Vega.
Correspondence: Borwin Bandelow, Psychiatry and Psychotherapy, University of G ö ttingen, von-Siebold-Str. 5, D-37075 G ö ttingen, Germany. E-mail:
Borwin.Bandelow@medizin.uni-goettingen.de
(Received 12 August 2011 ; accepted 5 January 2012 )
REVIEW ARTICLE
Guidelines for the pharmacological treatment of anxiety disorders,
obsessive compulsive disorder and posttraumatic stress disorder
in primary care
BORWIN BANDELOW
1
, LEO SHER
2
, ROBERTAS BUNEVICIUS
3
, ERIC HOLLANDER
2
,
SIEGFRIED KASPER
4
, JOSEPH ZOHAR
5
, HANS-J Ü RGEN M Ö LLER
6
, WFSBP TASK
FORCE ON MENTAL DISORDERS IN PRIMARY CARE
a
AND WFSBP TASK FORCE ON
ANXIETY DISORDERS , OCD AND PTSD
b
1
Department of Psychiatry and Psychotherapy, University of G ö ttingen, G ö ttingen, Germany,
2
Albert Einstein College of
Medicine and Montefi ore Medical Center, New York City, NY, USA,
3
Institute of Psychophysiology and Rehabilitation,
Lithuanian University of Health Sciences, Palanga, Lithuania,
4
Department of Psychiatry and Psychotherapy, Medical
University of Vienna, Vienna, Austria,
5
Division of Psychiatry, Chaim-Sheba Medical Center, Tel-Hashomer, Ramat Gan,
Israel, and
6
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
Abstract
Objective. Anxiety disorders are frequently under-diagnosed conditions in primary care, although they can be managed
effectively by general practitioners. Methods. This paper is a short and practical summary of the World Federation of
Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety disorders, obsessive compulsive
disorder (OCD) and posttraumatic stress disorder (PTSD) for the treatment in primary care. The recommendations were
developed by a task force of 30 international experts in the fi eld and are based on randomized controlled studies.
Results. First-line pharmacological treatments for these disorders are selective serotonin reuptake inhibitors (for all disor-
ders), serotonin-norepinephrine reuptake inhibitors (for some) and pregabalin (for generalized anxiety disorder only).
A combination of medication and cognitive behavior/exposure therapy was shown to be a clinically desired treatment
strategy. Conclusions. This short version of an evidence-based guideline may improve treatment of anxiety disorders, OCD,
and PTSD in primary care.
Key Words:
Anxiety disorders , guidelines , panic disorder , generalized anxiety disorder , social anxiety disorder , pharmacological
treatment
Introduction
Anxiety disorders are frequently under-diagnosed
conditions in primary care, although they can be
managed effectively by general practitioners. The
World Health Organization (WHO) and American
Psychiatric Association (APA) developed specifi c
diagnostic guidelines for the mental disorders in
primary care. This publication is a complementary
tool a brief and user friendly diagnostic guideline,
developed for general practitioners. It is a short
and practical summary of the WFSBP guidelines
for the anxiety disorders, obsessive compulsive
disorder (OCD) and posttraumatic stress disorder
International Journal of Psychiatry in Clinical Practice, 2012; Early Online: 1–8
ISSN 1365-1501 print/ISSN 1471-1788 online © 2012 Informa Healthcare
DOI: 10.3109/13651501.2012.667114
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
2 B. Bandelow et al.
(PTSD) [1], aiming at providing information about
how to use modern medications for managing anx-
iety disorders in a busy primary care setting.
Although the lifetime prevalence of anxiety dis-
orders has remained stable over the last decade
about 29% the rate of treatment increased, along
with the increased awareness about anxiety disor-
ders, and the desire to improve quality of life.
Patients with anxiety disorders are frequent users
of emergency and primary medical services and are
at a high risk for suicide attempts and substance
abuse.
The current conceptualization of anxiety disor-
ders includes an interaction of a specifi c neurobio-
logical vulnerability (genetic, childhood adversity)
and environmental factors (stress, trauma). Anxiety
disorders are associated with dysfunction of sero-
tonin, norepinephrine and other neurotransmitter
systems.
Treatment
The WFSBP Task Force conducted a computer-
based literature research in order to identify all rel-
evant studies showing superiority to placebo and
superiority or equivalent effi cacy compared with
established comparator treatments. The studies had
to fulfi ll certain quality requirements. The categories
of evidence are shown in Table I and are based on a
systematic analysis of 510 randomized controlled
studies. Recommendation grades are based on a
synthesis of evidence and the risks of a drug (for
example, benzodiazepines have category of evidence
A, but only a recommendation grade of 2, due to
their addiction potential).
Treatment is indicated in the majority of patients
who fulfi ll the WHO International Classifi cation of
Diseases (ICD-10) or APA Diagnostic and Statistical
Manual (DSM-IV-TR) criteria for an anxiety disor-
der, OCD or PTSD (Table II). The treatment plan
is based on the patient s preference, severity of ill-
ness, co-morbidity, concomitant medical illnesses,
complications like substance abuse or suicide risk,
the history of previous treatments, cost issues and
availability of types of treatment in a given area.
Treatment options include drug treatment and psy-
chological therapy. Before drug treatment is initiated,
it is strongly recommended that the mechanisms
underlying psychic and somatic anxiety be explained
to the patient (brochures that explain the typical fea-
tures of the patient’s condition, treatment options,
and adverse drug effects might be useful). Compli-
ance with drug treatment can be improved when
the advantages and disadvantages of the drugs are
explained carefully.
Treatment should continue for at least 6 24
months after remission has occurred, in order to
reduce the risk of relapse, and may be stopped only
if all, or almost all, symptoms disappear.
Drug treatment: available compounds
Selective serotonin reuptake inhibitors (SSRIs),
serotonin-norepinephrine reuptake inhibitors
(SNRIs), and pregabalin are recommended as fi rst-
line drugs due to their favorable risk-benefi t ratio,
with some differentiation regarding the various anx-
iety disorders (Table III).
SSRIs . SSRIs are indicated for the anxiety disor-
ders, OCD, and PTSD. Although treatment with
Table I. Categories of evidence and recommendation grades (Table III gives the categories of
evidence for all recommended drugs). For a detailed defi nition of the evidence and recommendation
grades, see [1].
Category of evidence Description
A Full evidence from controlled studies
B Limited positive evidence from controlled studies
C Evidence from uncontrolled studies or case reports/expert opinion
C1 Uncontrolled studies
C2 Case reports
C3 Based on the opinion of experts in the fi eld or clinical experience
D Inconsistent results
E Negative evidence
F Lack of evidence
Recommendation grade Based on:
1 Category A evidence and good risk-benefi t ratio
2 Category A evidence and moderate risk-benefi t ratio
3 Category B evidence
4 Category C evidence
5 Category D evidence
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
WFSBP guidelines for primary care 3
SSRIs is usually well tolerated, restlessness, jitteri-
ness, an increase in anxiety symptoms, insomnia or
headache in the fi rst days or weeks of treatment may
jeopardize compliance with treatment. Lowering the
starting dose of SSRIs may reduce this overstimula-
tion. Other side effects include nausea (and therefore
the recommendation is to take it after a meal), head-
ache, fatigue and dizziness. The anxiolytic effect may
start with a delay of 2 4 weeks (in some cases up to
6 or 8 weeks). Long term side effects include sexual
dysfunctions and weight gain.
SNRIs. The anti-anxiety effect of SNRIs may have a
latency of 2 4 weeks. Like SSRIs, at the beginning of
treatment, side effects like nausea, restlessness, insom-
nia or headache may pose a threat to compliance with
treatment. Also, sexual dysfunctions, discontinuation
syndromes, increased blood pressure, and other
adverse events have been reported. There is no suffi -
cient evidence to support the use of SNRIs in OCD.
Pregabalin . The calcium channel modulator pregaba-
lin has been found to be effective in GAD . The
anxiolytic effects of the drug are attributed to its
binding at the α
2
- δ -subunit protein of voltage-gated
calcium channels in central nervous system tissues.
Such binding reduces calcium infl ux at nerve termi-
nals and modulates the release of neurotransmitters.
The main side effects include dizziness and somno-
lence. The onset of effi cacy occurs in the fi rst days
of treatment, which is an advantage over treatment
with antidepressants.
TCAs. The effi cacy of TCAs in panic disorder and
generalized anxiety disorder is well proven, mainly
for imipramine and clomipramine. However, TCAs
have not been investigated systematically in social
anxiety disorder. Compliance may be reduced by
adverse effects such as sedation, prolonged reaction
time, dry mouth, constipation and weight gain. Phar-
macokinetic interactions can limit their use in patients
taking concomitant medication. However, the major
consideration is their potential lethality in case of
overdose, due to their potential cardiac and CNS
toxicity. Hence, TCAs should be avoided in patients
at risk of suicide. Moreover, in general, the frequency
Table II. Short description of anxiety disorders as defi ned by ICD-10 [2] and DSM-IV-TR [3].
Panic disorder (PD)
Panic disorder is characterized by recurrent panic attacks. Panic attacks are discrete periods of intense fear or discomfort, accompanied
by at least four somatic and psychic symptoms (palpitations, sweating, trembling, dyspnoea, choking sensations, chest pain, nausea,
abdominal distress, dizziness, feeling of unreality, fear of dying, etc.). A panic attack reaches a peak within 10 min and lasts 30 45
min on average. Usually, the patient is afraid that he has a serious medical condition such as myocardial infarction.
Agoraphobia
About two-thirds of all patients with panic disorder suffer from agoraphobia, which is defi ned as fear in places or situations from which
escape might be diffi cult or in which help may not be available in the event of having an unexpected panic attack. These situations
include being in a crowd or standing in a line, being outside the home alone, or traveling in a bus, train or automobile. These
situations are avoided or endured with marked distress.
Generalized anxiety disorder (GAD)
The main features of generalized anxiety disorder are excessive anxiety and worry. The patients suffer from somatic anxiety symptoms
as well as from restlessness, irritability, diffi culty concentrating, muscle tension, sleep disturbances and being easily fatigued. Patient
may express constant worry that the patient or a relative will shortly become ill or have an accident.
Specifi c phobia
Specifi c phobia is characterized by excessive or unreasonable fear of single objects or situations (e.g., ying, heights, animals, seeing
blood, etc.).
Social phobia (social anxiety disorder; SAD)
This disorder is characterized by marked, persistent, and unreasonable fear of being observed or evaluated negatively by others in social
performance or interaction situations and is associated with somatic and cognitive symptoms. The feared situations are avoided or
else are endured with intense anxiety or distress. These situations include fear of speaking in public, speaking to unfamiliar people or
being exposed to possible scrutiny by others.
Obsessive-compulsive disorder (OCD)
OCD is characterized by recurrent obsessions or compulsions, or both, that cause impairment in terms of distress, time, or interference
with functioning. Concerns involving contamination, harm, hoarding, and sexual, somatic and religious preoccupations are the most
common obsessions. Compulsions include washing, checking, repeating, ordering, counting, hoarding and touching (rare).
Post-traumatic stress disorder (PTSD)
PTSD develops after a terrifying ordeal that involved physical harm or the threat of physical harm. The person who develops PTSD
may have been the one who was harmed, the harm may have happened to a loved one, or the person may have witnessed a harmful
event that happened to loved ones or strangers. The condition is characterized by recurrent and intrusive distressing recollections of
the event, nightmares, a sense of reliving the experience with illusions, hallucinations, or dissociative fl ashback episodes, intense
psychological or physiological distress at exposure to cues that resemble the traumatic event, avoidance of stimuli associated with the
trauma, inability to recall important aspects of the trauma, loss of interest, estrangement from others, sleep disturbances, irritability,
diffi culty concentrating, hypervigilance, and exaggerated startle response. The full symptom picture must be present for more than
1 month.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
4 B. Bandelow et al.
of adverse events is higher for TCAs than for newer
antidepressants, such as the SSRIs or SNRIs. Thus,
the latter drugs should be tried fi rst before TCAs are
used.
Benzodiazepines. The anxiolytic effect starts within
minutes after oral or parenteral application. In
general, they have a good record of safety. Due to
CNS depression, benzodiazepine treatment may be
associated with sedation, dizziness, and prolonged
reaction time. Accordingly, cognitive functions and
driving skills are affected. After a couple of weeks or
months of continuous treatment with benzodia-
zepines, low-dose dependency may occur in a sub-
stantial number of patients. Patients with a history
of benzodiazepine, alcohol or other psychoactive
substance abuse should generally be excluded from
treatment, or be closely monitored in specialized
care settings. Benzodia-zepines may also be used in
combination with serotonergic medications during
the fi rst weeks of treatment to suppress increased
anxiety. In general, benzodiazepines should be used
with a regular dosing regimen. Only in the treatment
of short-term distress (e.g., air travel or dental pho-
bia), p.r.n. (when necessary) use may be justifi ed.
One should be aware that benzodiazepines were not
found to be effective in acute stress disorder and in
conditions with depression comorbidity, or OCD.
Antihistamines . The antihistamine hydroxyzine is
effective in generalized anxiety disorder. Because of
sedating effects, the antihistamine should only be
Table III. Recommendations for drug treatment of anxiety disorders and OCD. Daily dose in mg (in brackets: categories of evidence and
recommendation grade: see Table I.
Panic disorder
Generalized
anxiety
disorder
Social
anxiety
disorder
Obsessive-
compulsive
disorder
Post-traumatic
stress disorder
Selective Serotonin Reuptake Inhibitors (SSRIs)
Citalopram 20 60 (A; 1) 20 40 (B; 3)
Escitalopram 10 20 (A; 1) 10 20 (A; 1) 10 20 (A; 1) 10 20 (A; 1)
Fluoxetine 20 40 (A; 1) 20 40 (D; 5) 20 60 (A; 1) 20 40 (A; 1)
Fluvoxamine 100 300 (A; 1) 100 300 (A; 1) 100 300 (A; 1)
Paroxetine 20 60 (A; 1) 20 50 (A; 1) 20 50 (A; 1) 20 60 (A; 1) 20 40 (A; 1)
Sertraline 50 150 (A; 1) 50 150 (A; 1) 50 150 (A; 1) 50 200 (A; 1) 50 100 (A; 1)
Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
Venlafaxine 75 225 (A; 1) 75 225 (A; 1) 75 225 (A; 1) 75 –225 (A; 1)
Duloxetine 60 120 (A; 1)
Tricyclic Antidepressants
Amitriptyline 75 200 (B; 3)
Clomipramine 75 250 (A; 2) 75 300 (A; 2)
Imipramine 75 250 (A; 2) 75 200 (B; 3)
Calcium Channel Modulators
Pregabalin 150 600 (A; 1)
Gabapentin 600 3,600 (B; 3)
MAO Inhibitors
Phenelzine 45 90 mg (B; 3) 45 90 (A; 2) 45 90 (D; 5) 45 90 (D; 5)
Reversible Inhibitor of Monoaminoxidase A (RIMA)
Moclobemide 300 600 mg (D; 5)
Benzodiazepines
Alprazolam 1.5 8 (A; 2)
Clonazepam 1 4 (A; 2) 1.5 8 mg (B; 3)
Diazepam 5 20 (A; 2) 5 15 (A; 2)
Lorazepam 2 8 (A; 2) 2 8 (A; 2)
Atypical Antipsychotics
Quetiapine 50 300 (A; 1)
Risperidone 0.5 6 (B; 3)
Tricyclic Anxiolytic
Opipramol 50 150 (B;3)
Azapirone
Buspirone 15 60 (D; 5)
Noradrenergic and specifi c serotoninergic antidepressant (NasSA)
Mirtazapine 30 60 (B; 3) 30 60 (B; 3)
Antihistamine
Hydroxyzine 37.5 75 (A;2)
Abbreviations: see text. Not all drugs are currently approved in all countries for these indications; refer to local prescribing information.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
WFSBP guidelines for primary care 5
used when other medications have not been success-
ful or not tolerated. Side effects include sedation,
anticholinergic effects at high doses, blurred vision,
confusion, delirium and others. When sedating effects
are wanted, the antihistamine would be a better
option than benzodiazepines.
Atypical antipsychotics. In a number of studies, atyp-
ical antipsychotics such as quetiapine have been
used as monotherapy in GAD or as add-on treat-
ment for non-responsive cases of anxiety disorders,
OCD and PTSD. Side effects of atypical antipsy-
chotics include sedation, orthostatic hypotension,
sexual dysfunctions, metabolic syndrome, extrapy-
ramidal effects and others. However, in most coun-
tries atypical antipsychotics are not licensed for
these disorders. Therefore, treatment with these
medications should probably be reserved only to a
specialist setting.
Dosing
Approximately 75% of patients respond to the initial
low dose of antidepressants (with the exception of
OCD). In some patients, such as the elderly, treat-
ment should be started with half the recommended
dose or less in order to minimize initial adverse drug
events. In particular, patients with panic disorder
may be sensitive to serotonergic stimulation and
may easily discontinue treatment because of initial
jitteriness and nervousness. For tricyclic antidepres-
sants (TCAs), it is recommended to initiate the drug
at a low dose and increase the dose every 3 5 days.
The antidepressant dose should be increased to the
highest recommended therapeutic level if the initial
treatment with a low or medium dose fails. For
OCD, medium to high doses are recommended. If
pharmacokinetic data support once daily dosing,
taking medications in a single dose may increase
compliance. In patients with hepatic impairment, a
dosage adjustment or use of medications with pri-
marily renal clearance (e.g., pregabalin) may be
required.
If the patient does not respond to treatment in
an adequate dose after 4 6 weeks (8 12 weeks in
OCD or PTSD), medication should be changed or
a referral to a psychiatrist should be considered.
For patients who do not improve with standard
treatments, a number of alternative options exist,
including the addition of antipsychotics to the
antidepressant medication in OCD (for details
see [1].
In patients unresponsive to medications, the addi-
tion of cognitive behavioral therapy (CBT) may be
successful.
Non-pharmacological treatment
All patients with anxiety disorders require supportive
therapy. Psychological and pharmacological treat-
ments are often concomitant therapies, rather than
alternative therapies. Exposure therapy (e.g., gradual
exposure in vivo, ooding ) and response preven-
tion were found to be very effective in specifi c pho-
bia, agoraphobia, social phobia and OCD. However,
techniques like exposure and response prevention
have high rates of therapy refusal and attrition due
to unpleasant experience during sessions and related
anticipatory anxiety. As a rule, patients should be
transferred to experienced psychotherapists for for-
mal psychotherapy; however, physicians in primary
care also can help their patients with supportive talks,
by providing psychoeducational advice, and by
encouraging them not to avoid feared situations.
Choosing between medications and CBT is deter-
mined by a number of factors, particularly the
patient s preference, treatment options at hand,
adverse drug effects, onset of effi cacy, comorbidity
(e.g., with depression), nancial considerations, time
availability and commitment of the patient, accessi-
bility of psychiatric and psychological treatment
resources, and qualifi cation and experience of the
clinician.
Special treatment recommendations for the
different anxiety disorders
The treatment recommendations for the different
anxiety disorders are summarized in Table III. Some
antianxiety drugs are effective in all anxiety disor-
ders, whereas some drugs have only been studied in
specifi c anxiety disorders and thus should be reserved
for use in these particular disorders.
Panic disorder and agoraphobia . In acute panic attacks,
reassurance of the patient may be suffi cient in most
cases. In severe attacks, short-acting benzodiazepines
may be needed (e.g., melting tablets). SSRIs and
venlafaxine are the fi rst-line treatments for panic dis-
order. After remission, treatment should continue for
at least several months in order to prevent relapses.
SSRIs, venlafaxine, TCAs, benzodiazepines and
other drugs have shown long-term effi cacy in these
studies. Regarding SSRIs and SNRIs, the same doses
are usually prescribed in the maintenance treatment
as in the acute treatment phase.
A combination of CBT and medication treatment
has been shown to have the best treatment outcomes.
Exposure therapy is used to treat agoraphobia, and
CBT was developed for treating spontaneous panic
attacks. Exercise seems to have some effect in panic
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
6 B. Bandelow et al.
disorder; however, this effect seems to be less pro-
nounced than the effect of medication.
Generalized anxiety disorder (GAD) . The rst-line
treatments for GAD are SSRIs, SNRIs and pregaba-
lin. Other treatment options include buspirone and
hydroxyzine. Benzodiazepines should only be used
for long-term treatment when other drugs or CBT
have failed.
As a psychological treatment strategy, CBT and
associated techniques have been used in generalized
anxiety disorder. CBT is based on cognitive models
stressing the role of worrying, cognitions, and avoid-
ance behavior.
Social anxiety disorder (SAD) . First-line treatments
include SSRIs and venlafaxine. Benzodiazepines
have not been studies extensively in SAD, and there
is no evidence for the use of tricyclic antidepressants
in SAD. The irreversible monoamineoxidase inhibi-
tor phenelzine may be an option in treatment-
unresponsive cases. SAD is generally a chronic
disorder and requires long-term treatment.
Among psychological therapies, exposure therapy
and CBT have been shown to be effective.
Specifi c phobia . Usually, patients with specifi c phobia
do not consult medical professionals, especially if
they can cope with their phobia by avoiding the spe-
cifi c feared situations or objects. Exposure therapy is
effective to treat specifi c phobia. Psychopharmaco-
logical drugs are not recognized as a standard treat-
ment in simple cases of specifi c phobia. In severe
cases, SSRIs can be tried.
Obsessive compulsive disorder (OCD) . First-line treat-
ments are the SSRIs and the TCA clomipramine. It
is recommended to use the medium to upper dose
range (although the evidence regarding a dose-
response relationship for SSRIs and clomipramine
in OCD is mixed). OCD requires long-term treat-
ment at an effective dose-level ( The dose that
makes you well, keeps you well ). If patients do not
respond, consultation with a psychiatrist might be
considered. In severe OCD cases, where all other
available therapeutic approaches have been tried
without success, deep brain stimulation may be a
treatment option.
Post-traumatic stress disorder (PTSD) . First-line treat-
ments include the SSRIs and venlafaxine. PTSD is
often a chronic disorder and needs long-term treat-
ment for at least 12 24 months. Long-term effi cacy
was proven for the SSRIs fl uoxetine and sertraline
and the SNRI venlafaxine.
Only a minority (10 20%) of persons subject to
severe traumatic events develop PTSD. The current
recommendation in the fi rst month is summarized
by three Ps: Don’t Pathologize ( this is a normal
response to an abnormal situation ), Don’t Psycholo-
gize (don t facilitate emotional reaction via group
therapy, or stressful debriefi ng), and Don’t Pharma-
cologize (there is no evidence that prophylactic med-
ication treatment may prevent the development of
PTSD). CBT is indicated only several months after
exposure to trauma and for individuals who have
developed PTSD. Debriefi ng (a therapeutic con-
versation with an individual who has just experienced
a traumatic event in order to prevent PTSD) and
benzodiazepines in the fi rst few hours after exposure
is contraindicated, as they might interfere with the
potent spontaneous recovery process.
Treatment under special conditions
Pregnancy. The risks of drug treatment during preg-
nancy must be weighed against the risk of withhold-
ing treatment for an anxiety disorder. According to
the majority of studies, the use of SSRIs and TCAs
in pregnancy imposes no increased risk for malfor-
mations. It is recommended to avoid paroxetine
alprazolam use among pregnant women or women
planning to become pregnant.
Breast-feeding. SSRIs and TCAs are excreted into
breast milk, and low concentrations have been found
in infants serum. Plasma levels of the SSRIs parox-
etine and sertraline in breast-fed infants are usually
undetectable. In mothers receiving SSRIs and TCAs
(with the exception of doxepine), it seems unwar-
ranted to recommend that breast-feeding should be
discontinued. During maternal treatment with ben-
zodiazepines, infants should be observed for signs of
sedation, lethargy, poor suckling, and weight loss,
and if high doses have to be used and long-term
administration is required, breast feeding should
probably be discontinued.
Treating children and adolescents. Regarding the phar-
macological treatment of anxiety disorders, experi-
ence in children and adolescents suggests that SSRIs
should be the fi rst-line treatment. However, there
have been warnings against their use due to concerns
about increased risk of suicidal ideation and behav-
ior. Careful monitoring is advisable, due to possible
diagnostic uncertainty and the presence of co-
morbid depression.
Treating the elderly. Factors that should be regarded
in the treatment of the elderly include an increased
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
WFSBP guidelines for primary care 7
sensitivity for anticholinergic properties, an increased
risk for orthostatic hypotension, ECG changes dur-
ing treatment with TCAs, and possible paradoxical
reactions to benzodiazepines, which include depres-
sion, with or without suicidal tendencies, phobias,
aggressiveness, or violent behavior. Thus, treatment
with TCAs or benzodiazepines is less favorable, while
SSRIs appear to be safe.
Treatment of patients with severe somatic disease . Patients
with cardiovascular, cerebrovascular and endocrine
disease may have adequate and reasonable anxiety
reactions associated with their somatic disease state.
They may also suffer from comorbid primary anxiety
disorders. Such anxiety disorders are believed to
compound the management and the prognosis of
chronic obstructive pulmonary disease, coronary
artery disease or myocardial infarction, diabetes mel-
litus or brain injury. Anxiety symptoms may also be
a consequence of medical conditions, such as hyper-
thyroidism.
TCAs are best avoided in patients with cardiac
disease. By contrast, the SSRIs have modest effects
on cardiovascular function (although higher doses of
citalopram and escitalopram have been associated
with QT
C
prolongation) and may have potentially
benefi cial effects on platelet aggregation. Venlafaxine
is usually well tolerated, but blood pressure should
be monitored in patients with hypertension.
When should a patient be referred to
specialist care?
When a patient has been unresponsive after two tri-
als with fi rst-line medications, when the anxiety dis-
order is complicated by alcohol or substance abuse,
when the disorder substantially interferes with social
and occupational functioning of a patient or when
secondary depression or suicidality occur, the patient
should be referred to specialist care.
Conclusion
Patients with anxiety disorders, obsessive compul-
sive disorder and posttraumatic stress disorder may
be effectively treated in primary care. With adequate
treatment, the quality of life of patients with these
disorders may substantially be improved. A combina-
tion of CBT and medication treatment was shown
to have better treatment outcomes.
These principles of practice are considered guide-
lines only. Adherence to them will not ensure a suc-
cessful outcome in every case. The recommendations
are based on randomized controlled studies, which
do not always refl ect clinical reality. The individual
treatment of a patient should be planned in the light
of clinical features presented by the patient and the
diagnostic and treatment options available.
Key points
This short version of an evidence-based guide-
line may improve treatment of anxiety disorders,
OCD, and PTSD in primary care
First-line pharmacological treatments for these
disorders are selective serotonin reuptake inhibi-
tors (for all disorders), serotonin-norepinephrine
reuptake inhibitors (for some) and pregabalin
(for generalized anxiety disorder only)
A combination of medication and cognitive
behavior/exposure therapy was shown to be a
clinically desired treatment strategy
The recommendations are based on randomized
controlled studies, which do not always refl ect
clinical reality
Acknowledgements
None.
Statement of interest
The development of these guidelines was not sup-
ported by any pharmaceutical company. Borwin Ban-
delow has received grants/research support, consulting
fees and honoraria within the last 3 years from Astra-
Zeneca, Bristol-Myers-Squibb, Glaxo-SmithKline,
Jazz, Merck, Lilly, Lundbeck, Ono Pharma, Otsuka,
Pfi zer and Servier. Robertas Bunevicius has received
grants/research support, consulting fees and honoraria
within the last 3 years from Lundbeck, AstraZeneca,
Teva. Eric Hollander has received grant/research sup-
port, consulting fees and honoraria within the last
years from Abbott BMS, Janssen, Nastech, and Neu-
ropharm. Joseph Zohar has received grants/research
support, consulting fees and honoraria within the last
3 years from Glaxo-Smith Kline, Lundbeck, Pfi zer,
Servier, Teva and Wyeth. Siegfried Kasper received
grants/research support, consulting fees and honoraria
within the last three years from AstraZeneca, Bristol-
Myers Squibb, CSC, Eli Lilly, GlaxoSmithKline, Jans-
sen Pharmaceutica, Lundbeck, MSD, Novartis,
Organon, Pierre Fabre, Pfi zer, Schwabe, Sepracor,
Servier, Wyeth. Hans-J ü rgen M ö ller has received
grant/research support, consulting fees and honoraria
within the last years from AstraZeneca, Bristol-Myers
Squibb, Eli Lilly, GlaxoSmithKline, Janssen Cilag,
Lundbeck, MSD, Novartis, Organon, Otsuka, Pfi zer,
Schwabe, Sepracor, Servier, and Wyeth. Leo Sher:
nothing to disclose .
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
8 B. Bandelow et al.
References
Bandelow B, Zohar J, Hollander E, Kasper S, Moller HJ, [1]
Allgulander C, et al. World Federation of Societies of
Biological Psychiatry (WFSBP) guidelines for the pharma-
cological treatment of anxiety, obsessive-compulsive and
post-traumatic stress disorders rst revision. World J Biol
Psychiatry 2008;9(4):248 312.
WHO. World Health Organisation. Tenth Revision of the [2]
International Classifi cation of Diseases, Chapter V (F): Men-
tal and Behavioural Disorders (including disorders of psycho-
logical development). Clinical Descriptions and Diagnostic
Guidelines. Geneva: World Health Organisation; 1991.
APA. Diagnostic and statistical manual of mental disorders. [3]
4th ed. Text revision (DSM-IV-TR
®
). Washington, DC:
American Psychiatric Press; 2000.
    • "Available pharmacological and psychotherapeutic treatments (Bandelow et al., 2007) which aim to reduce fear and anxiety are associated with decreased symptom severity, but up to 40% of anxiety patients show only partial long-term benefit, and a majority of them fail to achieve complete remission (Hoffman & Mathew, 2008; Stein et al., 2009; Bandelow et al., 2012) clearly underlining the need for further improvement. Current pharmacological approaches either induce rapid anxiolytic effects (e.g. "
    [Show abstract] [Hide abstract] ABSTRACT: Pathological fear and anxiety are highly debilitating and, despite considerable advances in psychotherapy and pharmacotherapy they remain insufficiently treated in many patients with PTSD, phobias, panic and other anxiety disorders. Increasing preclinical and clinical evidence indicates that pharmacological treatments including cognitive enhancers, when given as adjuncts to psychotherapeutic approaches [cognitive behavioral therapy including extinction-based exposure therapy] enhance treatment efficacy, while using anxiolytics such as benzodiazepines as adjuncts can undermine long-term treatment success. The purpose of this review is to outline the literature showing how pharmacological interventions targeting neurotransmitter systems including serotonin, dopamine, noradrenaline, histamine, glutamate, GABA, cannabinoids, neuropeptides (oxytocin, neuropeptides Y and S, opioids) and other targets (neurotrophins BDNF and FGF2, glucocorticoids, L-type-calcium channels, epigenetic modifications) as well as their downstream signaling pathways, can augment fear extinction and strengthen extinction memory persistently in preclinical models. Particularly promising approaches are discussed in regard to their effects on specific aspects of fear extinction namely, acquisition, consolidation and retrieval, including long-term protection from return of fear (relapse) phenomena like spontaneous recovery, reinstatement and renewal of fear. We also highlight the promising translational value of the preclinial research and the clinical potential of targeting certain neurochemical systems with, for example D-cycloserine, yohimbine, cortisol, and L-DOPA. The current body of research reveals important new insights into the neurobiology and neurochemistry of fear extinction and holds significant promise for pharmacologically-augmented psychotherapy as an improved approach to treat trauma and anxiety-related disorders in a more efficient and persistent way promoting enhanced symptom remission and recovery.
    Full-text · Article · Dec 2014
    • "Considering the neurobiology of GAD, pharmacological guidelines recommend treatment with selective serotonin reuptake inhibitors, selective serotonin– norepinephrine reuptake inhibitors, or pregablin (Montgomery et al., 2006; Hoffman and Mathew, 2008; Baldwin et al., 2012; Bandelow et al., 2012). Approved selective serotonin reuptake inhibitors for GAD include escitalopram (Davidson et al., 2004; Allgulander et al., 2006; Lenze et al., 2009) and paroxetine (Pollack et al., 2001; Rickels et al., 2003; Stocchi et al., 2003). "
    [Show abstract] [Hide abstract] ABSTRACT: This was a flexible-dosed study to evaluate the efficacy and safety of duloxetine 30-120 mg once daily in the treatment of generalized anxiety disorder (GAD) in older adult patients. Patients with GAD, who were at least 65 years of age, were randomly assigned to double-blind treatment with either duloxetine (N = 151) or placebo (N = 140). The primary efficacy measure was the Hamilton Anxiety Rating Scale (HAM-A) total score, and the primary endpoint was at week 10. Global functioning was assessed by the Sheehan Disability Scale (SDS). Safety and tolerability was assessed by the occurrence of treatment-emergent adverse events, serious adverse events, laboratory analyses, and vital signs. Analyses were conducted on an intent-to-treat basis. The overall baseline mean HAM-A total score was 24, and SDS global score was 14. Completion rates were 75% for placebo and 76% for duloxetine. At week 10, duloxetine was superior to placebo on mean changes from baseline in HAM-A total scores (-15.9 vs. -11.7, p < 0.001) and in SDS global scores (-8.6 vs. -5.4, p < 0.001). Treatment-emergent adverse events occurred in ≥5% of duloxetine-treated patients and twice the rate than with placebo including constipation (9% vs. 4%, p = 0.06), dry mouth (7% vs. 1%, p = 0.02), and somnolence (6% vs. 2%, p = 0.14). Duloxetine treatment was efficacious in the improvement of anxiety and functioning in older adult patients with GAD, and the safety profile was consistent with previous GAD studies. © 2014 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.
    Full-text · Article · Sep 2014
    • "Most pharmacological guidelines suggest that first-line pharmacotherapy should include selective serotonin reuptake inhibitors (SSRIs) and, more recently, venlafaxine extended-release, a serotonin norepinephrine reuptake inhibitor (SNRI), has also been identified as a promising agent for the treatment of PTSD (American Psychiatric Association, 2004; Baldwin et al., 2005; Bandelow et al., 2012; Canadian Psychiatric Association, 2006; Schaffer et al., 2012). However, the current pharmacotherapy options for PTSD often do not result in satisfactory clinical outcomes, as evidenced by several controlled or open-label clinical trials and a handful of metaanalyses that used various selection criteria (Ipser and Stein, 2012; Pae et al., 2008a; Watts et al., 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: Despite the fact that the majority of currently available treatment guidelines propose antidepressants as the first-line pharmacological therapy for posttraumatic stress disorder (PTSD), a substantial portion of patients fail to show an adequate response following this type of treatment. In this context, a number of small, open-label studies and randomized controlled clinical trials (RCTs) have found atypical antipsychotics (AAs) to be a beneficial treatment for patients with PTSD. Thus, the present meta-analysis was conducted to enhance the sample size power and further the current understanding of the role of AAs for the treatment of PTSD. An extensive search of several databases identified 12 appropriate RCTs and available data from 9 of these (n = 497) were included in the final meta-analysis. AAs may have potential benefits for the treatment of PTSD as indicated by changes from baseline of the total score on the Clinician Administered PTSD Scale (CAPS; standardized mean difference [SMD] = -0.289, 95% confidence intervals [CIs] = -0.471, -0.106), P = 0.002). Additionally, AAs were found to be significantly more effective (P < 0.0001) than a placebo in terms of change from baseline for the intrusion sub-score on the CAPS (SMD = -0.373, 95% CIs = -0.568, -0.178) but there were no significant reductions for the avoidance and hyperarousal sub-symptoms. The responder rate and rate of improvement of depressive symptoms were also significantly higher in the AA group than the placebo group (P = 0.004 and P < 0.0001, respectively). However, the present results should be interpreted carefully and be translated into clinical practice only with due consideration of the limited quality and quantity of existing RCTs included in this analysis.
    Full-text · Article · May 2014
Show more

    Recommended publications

    Discover more