World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders – Version 3. Part I: Anxiety disorders

For anxiety disorders, the average pre-to-post improvement in waitlist arms is a small effect, Cohen's d = 0.2.

“For anxiety disorders, the average pre-to-post gain in waitlist arms was Cohen's d = 0.2 (defined as a”

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In waitlist studies, most patients do not show substantial improvement.

“However, in reality, in waitlist studies, most patients do not show any substantial improvement.”

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Among the 200 waitlist comparisons evaluated in this guideline, only 12.5% had a negative result.

“Of the 200 comparisons with waitlists evaluated in this guideline, only 12.5 % showed a negative result.”

Nonblinded assessors exaggerate effect size by 68%.

“It was found that nonblinded assessors exaggerate the effect size by 68% (Hrobjartsson et al. 2013).”

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The systematic search included 1007 randomised controlled trials.

“A total of 1007 RCTs was included.”

In the vast majority of pure psychotherapy studies, patients were not excluded when they were taking medication.

“In the vast majority of”

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In depression trials, waitlist-arm improvements were significantly smaller than those in no-treatment conditions.

“Improvements seen in waitlist arms were even significantly smaller than in”

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In anxiety disorders, psychological placebos have significantly smaller average pre-to-post effect sizes (d = 0.83) than pill placebos (d = 1.29).

“A meta-analysis of RCTs in anxiety disorders (Bandelow et al. 2015) demonstrated that the average pre-to-post effect sizes of such psychological placebos are significantly smaller (Cohen' d=0.83) than those of pill placebos (d=1.29).”

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In many evaluated studies comparing two or more active treatments, the sample sizes were too small for a non-inferiority comparison.

“In a substantial number of evaluated studies which compared two or more active treatments, the sample sizes were too small for a non-inferiority comparison.”

Pill placebo treatment is associated with a large pre-to-post change of about d = 1.3.

“In contrast, pill placebo treatment is associated with a large pre-to-post change of around d = 1.3.”

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Drug trials were significantly shorter than psychotherapy studies.

“Drug trials were significantly shorter than psychotherapy studies.”

Among patients with PDA, 31% showed persistence of the disorder after 30 years.

“Of patients with PDA, 31 % showed a persistence of this disorder after this time period.”

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Substantial heritability of anxiety disorders was found in twin studies.

“Substantial heritability was found in twin studies (Bandelow et al. 2016).”

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In treatment-naive patients, a reduction of at least 20% of OCD symptom severity at week 4 was the best predictor of treatment response at 12 weeks.

“an open-label trial of fluoxetine in treatment-naive patients indicated that a reduction of at least 20% of OCD symptom severity at week 4 was the best predictor of treatment response at 12 weeks (da Conceicao Costa et al. 2013).”

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Long-term and relapse prevention studies have usually used the same dose levels as acute studies.

“Long-term and relapse prevention studies have usually been conducted with the same dose levels as in the acute studies.”

No biomarker has yet proven sufficiently sensitive and specific for anxiety disorders.

“Despite the extent and rigor of research on the neurobiology of these disorders, no biomarker has to date proven sufficiently sensitive and specific (Bandelow et al. 2016;Bandelow et al. 2017).”

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Anxiety disorders tend to have a chronic course.

“Anxiety disorders tend to have a chronic course.”

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In randomised controlled trials, approximately 75% of patients respond to the initial low dose of SSRIs or SNRIs, except in OCD.

“In RCTs, approximately 75% of patients respond to the initial (low) dose SSRIs/SNRIs (with the exception of OCD).”

Among patients with GAD, 58% still had the diagnosis after 30 years.

“A study evaluating the long-term outcomes found that of patients with GAD, 58% still had this diagnoses after 30 years (Tyrer et al. 2021).”

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Only half of psychotherapy studies used intent-to-treat analyses for missing data.

“Only in half of the psychotherapy studies, intent-to-treat (ITT) analyses were used for missing data.”

Controlled data on switching medications for anxiety disorders are lacking.

“Controlled data on switching medications are lacking for the anxiety disorders.”

In a study of 73 patients on clonazepam for at least 3 years, clonazepam could be successfully discontinued without major discontinuation symptoms.

“In a study with 73 patients receiving the benzodiazepine clonazepam for at least 3 years, it was found that clonazepam could be successfully discontinued (decreasing by 0.5 mg per 2-week period until 1 mg/day was reached, followed by a decrease of 0.25 mg per week) without any major discontinuation symptoms (Nardi et al. 2010).”

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Benzodiazepine anxiolytic effect starts within 30-60 minutes after oral or parenteral application.

“The anxiolytic effect starts within 30-60 minutes after oral or parenteral application.”

Frequency and burden of adverse events is higher for TCAs than for SSRIs or SNRIs.

“In general, the frequency and burden of adverse events is higher for TCAs than for the SSRIs or SNRIs.”

Efficacy of venlafaxine and duloxetine in certain anxiety disorders has been shown in controlled studies.

“The efficacy of the SNRIs venlafaxine and duloxetine in certain anxiety disorders has been shown in several controlled studies (see below for references).”

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Efficacy of phenelzine has been shown in some controlled studies in PDA, SAD and PTSD.

“The efficacy of the irreversible MAOI phenelzine has been shown in some controlled studies in PDA, SAD and PTSD (see below for references).”

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After long-term benzodiazepine treatment over 2-8 months, tolerance to therapeutic dose may occur in some patients.

“After long-term treatment with benzodiazepines (e.g. over 2-8 months), tolerance to the therapeutic dose may occur in some patients (Nelson and Chouinard 1999).”

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TCAs have potential cardiac and CNS toxicity after overdose.

“TCAs should be avoided in patients considered at risk of suicide, due to their potential cardiac and CNS toxicity after overdose (Nutt 2005).”

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Atypical paradoxical reactions in elderly patients treated with benzodiazepines are rare, around 1%.

“Atypical (paradoxical) reactions in elderly patients treated with benzodiazepines are rare (around 1 %) (Mancuso et al. 2004).”

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TCAs have not been investigated systematically in SAD.

“TCAs have not been investigated systematically in the treatment of SAD.”

The anxiolytic effect of SSRIs may start with a delay of 2-4 weeks, in some cases up to 6-8 weeks.

“The anxiolytic effect may start with a delay of 2-4 weeks (in some cases up to 6 or 8 weeks).”

Phenelzine is used mostly by experienced psychiatrists when other treatments have been unsuccessful or not tolerated.

“It is used mostly by experienced psychiatrists when other treatment modalities have been unsuccessful or have not been tolerated.”

TCAs may reduce compliance due to adverse effects such as initially increased anxiety, dry mouth, amblyopia, postural hypotension, tachycardia, sedation, and impaired psychomotor function.

“Especially at the beginning of treatment, compliance may be reduced by adverse effects such as initially increased anxiety symptoms, dry mouth, amblyopia, postural hypotension, tachycardia, sedation, impaired psychomotor function/car driving safety, and others.”

The antianxiety effect of SNRIs may have a latency of two to four weeks, sometimes longer.

“The antianxiety effect of SNRIs may have a latency of two to four weeks, and in some cases this latency may even be longer.”

Tolerance is probably more common in predisposed patients with history of alcohol or drug abuse or personality disorders.

“This is probably more common in predisposed patients, e.g. with a history of alcohol or drug abuse or personality disorders (Romach et al. 1995;Schweizer et al. 1998).”

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In treatment-resistant cases, phenelzine may be very useful.

“However, in these cases, it may be very useful (Chamberlain and Baldwin 2021).”

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In patients with suicidal ideation, benzodiazepines may provide fast symptom control.

“In patients with suicidal ideation, they may provide fast symptom control.”

Efficacy of benzodiazepines in anxiety disorders has been shown in many controlled clinical studies.

“The efficacy of benzodiazepines in anxiety disorders has been shown in many controlled clinical studies (see below for references).”

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TCAs have many pharmacokinetic interactions due to broad receptor profiles.

“Due to the broad receptor profiles of these drugs, many pharmacokinetic interactions can limit their use in patients taking concomitant medication.”

Benzodiazepines do not lead to initially increased anxiety or agitation, unlike antidepressants.

“In contrast to antidepressants, they do not lead to initially increased anxiety or agitation.”

Only one DBPC study supports use of mirtazapine in SAD.

“There is only on DBPC study supporting the use of mirtazapine in SAD.”

Pregabalin has been used in very high doses by individuals with multi-substance abuse, including snorting.

“According to case reports, pregabalin has been used in very high doses by individuals with multi-substance abuse, including snorting (Gahr et al. 2013;Schwan et al. 2010).”

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There are only a few case reports of persons who misused pregabalin alone but were not addicted to other substances.

“There are only a few case reports of persons who misused pregabalin alone but were not addicted to other substances (Driot et al. 2016;Halaby et al. 2015).”

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Efficacy of TCAs amitriptyline, clomipramine, imipramine in anxiety disorders, OCD and PTSD is well established.

“The efficacy of the TCAs amitriptyline, clomipramine, imipramine in anxiety disorders, OCD and PTSD is well established (see below for references).”

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Withdrawal of benzodiazepines is often challenging.

“Withdrawal of benzodiazepines is often challenging (Baldwin 2022).”

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SIADH may be a problem mainly in elderly patients with SSRIs.

“The syndrome of inappropriate ADH secretion (SIADH) may be a problem mainly in elderly patients (Bouman et al. 1998).”

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Pregabalin withdrawal symptoms have been reported, including nausea, diarrhea, headache, seizures, spasticity, nightmares, sleep disturbances, numb or tingling feelings, dizziness, anxiety, diaphoresis, tachycardia, and hallucinations.

“Withdrawal symptoms have been reported, including nausea, diarrhea, headache, seizures spasticity, nightmares, sleep disturbances, numb or tingling feelings, dizziness, anxiety, diaphoresis, tachycardia, hallucinations and others.”

Tolerance to anxiolytic or other effects seems to be rare according to long-term controlled trials.

“Tolerance to anxiolytic or other effects seems to be rare, according to long-term controlled trials (Nagy et al. 1989;Pollack et al. 1993;Rickels 1982;Worthington et al. 1998).”

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RCTs with tranylcypromine and other MAOIs fulfilling guideline criteria were not found.

“RCTs with tranylcypromine and other MAOIs which fulfilled the criteria of this guideline were not found.”

According to a review, the optimum duration of psychotherapy (all forms) is between 4 and 24 sessions.

“According to a review, the optimum duration of psychotherapy (all forms) is between 4 and 24 sessions (Robinson et al. 2020).”

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Anticonvulsants had shown efficacy in preliminary studies.

“Anticonvulsants, including carbamazepine, valproate, lamotrigine, topiramate and gabapentin had shown efficacy in preliminary studies and deserve further research.”

In depressed patients, dropout rates were lower when benzodiazepines were added to antidepressant treatment.

“In depressed patients, dropout rates were lower when benzodiazepines were added to antidepressant treatment (Furukawa et al. 2002).”

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There were concerns regarding tardive side effects after year-long antipsychotic treatment.

“Moreover, there were concerns regarding tardive side effects after year-long treatment, which is often required in the treatment of anxiety disorders.”

Forms of CBT such as exposure therapy were found very effective for specific phobia, agoraphobia, and social anxiety disorder.

“Forms of CBT, such as exposure therapy (e.g.gradual exposure in vivo) were found to be very effective for specific phobia, agoraphobia, and social anxiety disorder.”

An analysis did not find evidence that longer therapies (24 sessions) are more effective than shorter ones (12 sessions) for anxiety disorders.

“An analysis of treatment duration of psychotherapies for anxiety disorders did not find evidence from controlled studies that longer therapies (e.g.24 sessions) are more effective than shorter ones (e.g. 12 sessions) (Bandelow et al. 2022).”

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Benzodiazepines were not found effective for comorbid depression or OCD.

“When treating anxiety disorders, one should be aware that benzodiazepines were not found to be effective for frequently occurring comorbid conditions, such as depression or OCD.”

Buspirone is not effective in PDA.

“Buspirone is not effective in PDA.”

Only one DBPC study supports use of ketamine in SAD.

“There is only on DBPC study supporting the use of ketamine in SAD.”

Cognitive-behavioural interventions may facilitate benzodiazepine discontinuation.

“Cognitive-behavioural interventions may facilitate benzodiazepine discontinuation (Otto et al. 1993;Spiegel 1999).”

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Direct comparisons of psychotherapeutic and pharmacological interventions or their combination in randomised parallel group designs are rare.

“Direct comparisons of psychotherapeutic and pharmacological interventions or their combination in randomised parallel group designs are rare.”

Hydroxyzine does not generally play a role in current pharmacotherapy of GAD.

“The drug does not generally play a role in current pharmacotherapy of GAD.”

In 70% of available studies, psychological treatments have been compared to a waitlist which is not an adequate control condition.

“In 70 % of available studies, psychological treatments have been compared to a waitlist which is not an adequate control condition (see section 'Evidence grading in psychotherapy studies', p. 12).”

Studies comparing EMDR with or without eye movements did not find a difference.

“Studies comparing EMDR with or without eye movements did not find a difference (Boudewyns and Hyer 1996;Devilly et al. 1998).”

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Psychotherapy may also have side effects.

“Psychotherapy may also have side effects (Moritz et al. 2019).”

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Olanzapine and risperidone were effective in treatment-unresponsive patients with PTSD.

“Olanzapine and risperidone were effective in treatment-unresponsive patients with PTSD.”

Comparisons of massed vs. spaced CBT found equal efficacy.

“Comparisons of massed vs. spaced CBT found equal efficacy (Ehlers et al. 2014;Foa et al. 2018).”

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Only one study supports efficacy of trazodone in GAD.

“Only one study supports the efficacy of trazodone in GAD.”

Agomelatine was effective in treatment of GAD according to several studies.

“According to several studies, the melatonin MT1 and MT2 receptor agonist and 5-HT2C receptor antagonist agomelatine was effective in the treatment of GAD.”

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Atypical antipsychotics have been used as add-on treatment for non-responsive cases of anxiety disorders, OCD and PTSD.

“In several studies, atypical antipsychotics (including aripiprazole, olanzapine, and risperidone) have been used as add-on treatment for non-responsive cases of anxiety disorders, OCD and PTSD.”

Hydroxyzine was effective in GAD in several DBPC studies.

“The antihistamine hydroxyzine was effective in GAD in several DBPC studies (see below for references).”

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Buspirone may be effective for symptoms of GAD, as shown in some controlled studies.

“The partial 5 HT1A-agonist (azapirone) buspirone may be effective for symptoms of GAD, as shown in some controlled studies (see below for references).”

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Experience with long-term hydroxyzine treatment is lacking.

“Experience with long-term treatment is lacking.”

There is only one DBPC study supporting opipramol use in GAD.

“There is only one DBPC study supporting its use in GAD.”

Studies with antipsychotics in anxiety neuroses had methodological flaws.

“However, studies carried out with antipsychotics in patients suffering from 'anxiety neuroses' had some methodological flaws.”

Studies of benzodiazepines in PTSD are lacking.

“Although benzodiazepines are often used to treat acute stress reactions, studies in PTSD are lacking.”

Most meta-analyses comparing drugs and CBT examined treated-vs.-control effect sizes instead of pre-to-post effect sizes.

“Most meta-analyses comparing drugs and CBT examined treated-vs.-controleffect sizes instead of pre-to-post effect sizes.”

This results in a large treated vs. control effect size difference of Cohen's d = 1.1.

“This will result in a large treated vs. control effect size difference of Cohen's d = 1.1.”

Techniques like exposure and response prevention have high rates of therapy refusal and attrition due to unpleasant feelings and anticipatory anxiety.

“Techniques like exposure and response prevention have high rates of therapy refusal and attrition due to unpleasant feelings during sessions and related anticipatory anxiety.”

Similar placebo-controlled studies involved combination of imipramine and alprazolam or sertraline and clonazepam.

“Similar placebo-controlled studies involved a combination of imipramine and alprazolam (Woods et al. 1992) or of sertraline and clonazepam (Goddard et al. 2001).”

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When CBT fails, there are few alternative psychotherapy options.

“However, when CBT fails, there are few alternative psychotherapy options.”

In Europe, 57% of patients receiving psychotherapy are also on medication.

“In Europe, 57% of patients receiving psychotherapy are also on medication (Alonso et al. 2004b).”

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When a drug trial fails, several alternative medications can be used so patient can achieve remission after 2, 3, or 4 drugs.

“When a trial with a drug fails, there are several alternative medications which can be used so that the patient can achieve remission after 2, 3, or 4 drugs.”

Frequency of adverse events is higher for TCAs than for newer antidepressants such as SSRIs.

“However, the frequency of adverse events is higher for TCAs than for newer antidepressants, such as the SSRIs (Amore et al. 1999;Bakish et al. 1996;Bakker et al. 1999b;Bystritsky et al. 1994;Lecrubier and Judge 1997;Lepola et al. 1998;Wade et al. 1997) (LoE A/RG 2).”

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For desipramine and lofepramine, only one DBPC study exists.

“For desipramine and lofepramine, only one DBPC study exists (LoE B/RG 3).”

Medication adherence can be improved by using psychotherapeutic and psychoeducational methods.

“Medication adherence can be improved by using psychotherapeutic and psychoeducational methods (Zomahoun et al. 2017).”

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TCAs clomipramine and imipramine are as effective as SSRIs/SNRIs for PDA.

“The tricyclic antidepressants (TCAs) clomipramine and imipramine are as effective as the SSRIs/SNRIs.”

Evidence for the combination of psychotherapy and pharmacotherapy is stronger than against it.

“This is corroborated by the finding that evidence for the combination of both modalities is stronger than against it (for evidence from RCTs, see below).”

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In everyday clinical practice, both treatments are often combined.

“In everyday clinical practice, both treatments are often combined.”

A meta-analysis of follow-up studies revealed that psychotherapy, medications, and to a lesser extent placebo can produce enduring effects after termination.

“However, a meta-analysis of follow-up studies revealed that not only psychotherapy, but also medications and, to a lesser extent, placebo can produce enduring effects after termination (Bandelow et al. 2018).”

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No recommendation can be given for separation anxiety disorder in adults due to the lack of studies.

“For separation anxiety disorders in adults, no recommendation can be given due to the lack of studies.”

In treatment-refractory GAD, only adding olanzapine or pregabalin to an SSRI has demonstrated efficacy.

“Only the addition of olanzapine or pregabalin to an SSRI was shown to be effective in treatment-refractory cases.”

Our meta-analysis of studies comparing CBT with active controls showed a significant but small difference between CBT and active controls (Cohen's d = 0.23; CI 0.02-0.44; p=.035).

“Our meta-analysis of studies comparing CBT with active controls showed a significant but small difference between CBT and active controls (Cohen's d = 0.23; CI 0.02-0.44;p=.035; Figure 2, Supplementary Appendix) (LoE A/RG 1).”

Our meta-analysis of studies with active controls found no significant difference between CBT and active controls (Cohen's d = 0.15; 95% CI -0.05 to 0.35; p=.13; N.S.).

“Our meta-analysis of studies with active controls did not show a significant difference between CBT and active controls (Cohen's d = 0.15; -0.05-0.35);p=.13; N.S.) (Figure 7; Supplementary Appendix) (LoE D/RG 4).”

Clonazepam was effective in one placebo-controlled study for SAD.

“The benzodiazepines bromazepam and clonazepam were effective in one placebo-controlled study each; however, due to possible discontinuation symptoms, these medications should only be used second in line (LoE B/RG 2).”

A meta-analysis of follow-up studies found that improvements from cognitive behavioral therapy and other psychotherapies persisted for as long as 24 months after treatment ended.

“In this analysis, it was found that gains with CBT and other psychotherapies were maintained for up to 24 months.”

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Pregabalin was effective in randomized controlled trials for SAD.

“The calcium channel modulator pregabalin was effective in RCTs (LoE A/RG 2).”

For citalopram, only one double-blind placebo-controlled trial in SAD exists.

“For citalopram, only one DBPC study exists (LoE B/RG 2).”

Only two controlled trials have evaluated exercise as a treatment for panic disorder with agoraphobia.

“Only two controlled studies have been performed to assess the usefulness of exercise for PDA (Table 10).”

Phenelzine was shown to be effective for SAD.

“The MAOI phenelzine was shown to be effective; however, due to its unfavourable adverse effects profile and possible interactions with certain types of food and medications, the drug should only be used in otherwise treatment unresponsive patients (LoE A/RG 2).”

Gabapentin was effective in one study for SAD.

“Gabapentin was also effective in one study (LoE B/RG 2).”

For escitalopram, fluoxetine, duloxetine, and venlafaxine, there is one placebo-controlled study each.

“For the SSRIs escitalopram and fluoxetine and the SNRIs duloxetine and venlafaxine, one placebo-controlled study each is available (LoE B/RG 2).”

The sole double-blind placebo-controlled trial of buspirone in SAD found it ineffective.

“Buspirone was not effective in the only DBPC study (LoE B-/RG 2-).”

Fluvoxamine and sertraline, both SSRIs, were effective for treating generalized anxiety disorder and mixed anxiety disorders in children and adolescents.

“The SSRIs fluvoxamine and sertraline were effective in treating GAD/mixed anxiety disorders in children and adolescents (Table 12) (LoE A/RG 1).”

A meta-analysis found a significant difference between moclobemide and placebo in SAD, with a small effect size (Cohen's d = 0.33; CI 0.17-0.50; p<.0001).

“A meta-analysis of studies comparing moclobemide with placebo showed a significant difference between moclobemide and placebo (small effect size: Cohen's d = 0.33; CI 0.17-0.50;p<.0001; Figure 6; Supplementary Appendix) (LoE B/RG 2).”

Findings for moclobemide in SAD were inconsistent.

“The results with the reversible inhibitor of monoamine oxidase A (RIMA) moclobemide were inconsistent.”

A meta-analysis of GAD studies found benzodiazepines somewhat more efficacious than SSRIs or SNRIs.

“In a meta-analysis of GAD studies, benzodiazepines had somewhat greater efficacy than SSRIs/SNRIs (Gomez et al. 2018).”

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Only one randomized controlled trial of opipramol for GAD exists.

“However, only one RCT exists (LoE B/RG 3).”

One GAD study found psychodynamic therapy less effective than CBT.

“One GAD study showed it was less effective than CBT.”

In two double-blind placebo-controlled trials of SAD patients, atenolol did not demonstrate efficacy.

“The beta blocker atenolol failed to show efficacy in two DBPC studies with SAD patients (LoE A-/RG 1-).”

Citalopram was more effective than placebo in a study of elderly patients with GAD.

“Citalopram was only evaluated in a study with elderly patients, in which it was superior to placebo (LoE B/RG 2 for elderly patients).”

A second trial found no difference between venlafaxine plus CBT and venlafaxine alone.

“Another study found that adding CBT to venlafaxine did not differ from venlafaxine alone.”

Valproate was effective in a double-blind placebo-controlled study for GAD.

“The anticonvulsant valproate was shown to be effective in a DBPC study (LoE B/RG 3).”

In a single SAD trial, desvenlafaxine was indistinguishable from placebo.

“The SNRI desvenlafaxine did not differ from placebo in one study (LoE B-/RG 2-).”

No studies have shown psychodynamic therapy to be more effective than waitlist or psychological placebo for GAD.

“Studies showing that PdTh is more effective than waitlist or psychological placebo are lacking.”

Relapse prevention studies show that escitalopram, paroxetine, venlafaxine, duloxetine, pregabalin, agomelatine, quetiapine, and vortioxetine are more effective than placebo in preventing relapses in GAD.

“According to relapse prevention studies, treatment with escitalopram, paroxetine, venlafaxine, duloxetine, pregabalin, agomelatine, quetiapine and vortioxetine was more effective in preventing relapses than placebo (Table 11, Supplementary Appendix).”

In two SAD trials, moclobemide did not separate from placebo.

“The compound was superior to placebo in some studies, while it failed to separate from placebo in two studies.”

Bromazepam was effective in one placebo-controlled study for SAD.

“The benzodiazepines bromazepam and clonazepam were effective in one placebo-controlled study each; however, due to possible discontinuation symptoms, these medications should only be used second in line (LoE B/RG 2).”

The evidence for fluoxetine in SAD is inconclusive.

“The evidence for fluoxetine is inconclusive (LoE D/RG 4).”

One study that found iCBT equal to face-to-face CBT was underpowered.

“One study showing equal efficacy to face-to-face CBT was underpowered.”

Mirtazapine was effective in one study for SAD.

“The antidepressant mirtazapine was effective in one study (LoE B/RG 2).”

Some SAD studies found moclobemide superior to placebo.

“The compound was superior to placebo in some studies, while it failed to separate from placebo in two studies.”

The only study of internet psychodynamic therapy for GAD found no difference from waitlist.

“Internet psychodynamic therapy for GAD did not differ from a waitlist condition as demonstrated in the only available study (LoE B-/RG 2-).”

Agomelatine was effective in several double-blind placebo-controlled and comparator studies and in a relapse prevention study for GAD.

“The melatonin agonist/5-HT2C antagonist agomelatine was effective in several DBPC and comparator studies and a relapse prevention study (LoE A/RG 1).”

Ketamine (i.v.) was effective in one double-blind placebo-controlled study for SAD.

“The NMDA receptor antagonist ketamine (i.v.) was effective in one DBPC study (LoE B/RG 3).”

In a double-blind placebo-controlled trial with a very small sample, vilazodone for adult separation anxiety disorder did not differ from placebo.

“In a DBPC study with a very small sample size, vilazodone for adult separation anxiety disorder did not differ from placebo (Schneier et al. 2017).”

• cites Schneier et al. 2017Not checked yet

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Just two studies have compared combined CBT and medication against each monotherapy for GAD.

“Only two studies compared the combination of CBT and drug treatment with the monotherapies.”

Alprazolam, bromazepam, diazepam, and lorazepam are effective benzodiazepines for GAD.

“The benzodiazepines alprazolam, bromazepam, diazepam and lorazepam are effective, but are only recommended if first-line treatment with an SSRI or SNRI is ineffective or not tolerated (LoE A/RG 2).”

Moclobemide showed similar efficacy to phenelzine in SAD.

“It showed similar efficacy to phenelzine.”

Alprazolam was not superior to placebo in a double-blind placebo-controlled study.

“Alprazolam was not superior to placebo in a DBPC study (LoE B-/RG 2-).”

Some analyses found SSRIs exhibit efficacy for treatment of depression in children and adolescents.

“Some analyses found that SSRIs exhibited efficacy for treatment of depression in children and adolescents (Sharp and Hellings 2006) and found no significant increase in risk of suicide or serious suicide attempt after starting treatment with newer antidepressant drugs (Simon et al. 2006).”

• cites Sharp and Hellings 2006Not checked yet

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• cites Simon et al. 2006Not checked yet

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This review has shown that evidence for efficacy of psychotherapies for children and adolescents is not unequivocal for some disorders.

“This review has shown that evidence for the efficacy of psychotherapies for children and adolescents is not unequivocal for some disorders.”

Moclobemide combined with CBT is not superior to CBT alone.

“Combining moclobemide with CBT is not superior to CBT alone”

Moclobemide combined with CBT is more effective than moclobemide alone.

“but more effective than moclobemide alone”

Cognitive behavioral therapy for social anxiety disorder outperformed waitlist conditions.

“CBT for SAD was more effective than waitlist conditions.”

Placebo-treated patients in controlled maintenance studies experienced significantly more relapses.

“Controlled maintenance studies with a duration of 6-12 months also suggest treatment to be continued for this period, as significantly more relapses occurred in the patients treated with placebo.”

The evidence on combining CBT with medication for social anxiety disorder is inconclusive.

“Data on combining CBT and drugs for SAD are inconclusive (”

For dental phobia, CBT is superior to general anaesthesia.

“However, it was superior to general anaesthesia.”

In depressed patients on high dose venlafaxine, no clinical or statistically significant effects on ECG parameters were demonstrated.

“Another study of depressed patients on high dose venlafaxine (mean 346 mg; range 225-525 mg) did not demonstrate any clinical or statistically significant effects on electrocardiographic (ECG) parameters (Mbaya et al. 2007).”

• cites Mbaya et al. 2007Not checked yet

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One placebo-controlled study found the SSRI paroxetine to be effective.

“The SNRI venlafaxine and the SSRI paroxetine were effective in one placebo-controlled study each (LoE B/RG 2).”

One study found CBT to be more effective than fluoxetine.

“CBT was more effective than fluoxetine in one study.”

Only two of the 14 comparisons between CBT and active controls in SAD reached statistical significance.

“However, of 14 comparisons with active control conditions, only two showed a significant difference.”

Some studies have assessed D-cycloserine as an enhancer of exposure therapy or CBT for SAD.

“Some studies have evaluated the potential of D-cycloserine for enhancing the effects of exposure therapy or CBT for SAD (Table 19).”

One study found that iCBT differed from a psychological placebo.

“and one study showed that iCBT differed from a psychological placebo (LoE B/RG 2).”

The addition of psychodynamic therapy to clonazepam did not outperform clonazepam alone.

“Adding psychodynamic therapy to clonazepam was not more effective than monotherapy with clonazepam.”

For fear of flying, virtual reality exposure is superior to active controls.

“Virtual reality exposure was superior to active controls (LoE A/RG 1).”

SSRIs are effective medications for treating anxiety disorders and OCD in children and adolescents.

“SSRIs are effective medications for treating anxiety disorders and OCD in children and adolescents.”

CBT for selective mutism did not clearly separate from waitlist in available studies.

“It did not clearly separate from waitlist in the available studies; one study showed superiority to psychoeducation (LoE D/RG 3).”

One placebo-controlled study found the SNRI venlafaxine to be effective.

“The SNRI venlafaxine and the SSRI paroxetine were effective in one placebo-controlled study each (LoE B/RG 2).”

Sertraline plus CBT was not more effective than either monotherapy.

“Sertraline combined with CBT was not more effective than both monotherapies.”

In that meta-analysis, SSRIs had higher effect sizes than CBT.

“with higher effect sizes for SSRIs”

• cites Segool and Carlson 2008Not checked yet

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The FDA warning may have been off-set by reduced antidepressant prescriptions conducive to verified suicides in children and adolescents.

“However, the FDA warning may have been off-set by reduced antidepressant prescriptions conducive to verified suicides in children and adolescents (Gibbons et al. 2007).”

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For dental phobia, CBT is superior to hypnosis.

“It was also superior to hypnosis, which is not a validated treatment (LoE B/RG 2).”

Psychodynamic therapy was not superior to an active control.

“In comparison to an active control, it was not superior.”

Comparisons of iCBT with active control conditions are lacking.

“Comparisons with active controls are lacking.”

For certain specific phobias, a few exposure sessions totaling 1-5 hours are sufficient.

“A review of exposure treatments has shown that only a few sessions with an overall treatment length of 1-5 hours was sufficient to treat certain specific phobias (Bandelow et al. 2022).”

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In another study, virtual reality exposure therapy was less effective than in vivo exposure.

“and less effective in another”

In two of three studies, virtual reality exposure therapy outperformed waitlist.

“Virtual reality exposure therapy was superior to waitlist in 2 of 3 studies.”

D-cycloserine combined with exposure or CBT for specific phobias has no demonstrated effect.

“No effect of this combination could be demonstrated (LoE A-/RG 1-).”

Several comparison studies employed medications not considered first-line for SAD, such as phenelzine, moclobemide, and clonazepam.

“Some of the comparison studies have been conducted with drugs which are not firstline medications for SAD, including phenelzine, moclobemide and clonazepam.”

Small DBPC studies showed some effect of fluoxetine and sertraline for selective mutism.

“Small DBPC studies which do not fulfil the criteria of this guideline because of small sample sizes showed some effect of fluoxetine and sertraline (Barterian et al. 2018;Black and Uhde 1994;Carlson et al. 1999).”

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• cites Black and Uhde 1994Not checked yet

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• cites Carlson et al. 1999Not checked yet

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In one underpowered study, virtual reality exposure therapy was equally effective as in vivo exposure.

“In comparison to in vivo exposure, it was equally effective in one underpowered study”

Paroxetine is effective for specific phobias in a small double-blind placebo-controlled study.

“Paroxetine was effective in a small DBPC study in individuals with various specific phobias (LoE B/RG 2) (Table 15).”

Several studies found iCBT to be as effective as face-to-face CBT.

“In several studies, iCBT was as effective as face-to-face CBT.”

A double-blind placebo-controlled study demonstrated fluoxetine's efficacy.

“One double-blind placebo-controlled study showed efficacy of fluoxetine; however, it was less effective than CBT (LoE B/RG 3).”

Evidence for CBT for selective mutism is inconsistent.

“The evidence for CBT for selective mutism is inconsistent.”

A meta-analysis we performed on trials with active controls found a medium, significant difference between CBT and active controls (Cohen's d = 0.61; 95% CI 0.27-0.97; p=.001).

“Our meta-analysis of studies with active controls showed a medium significant difference between CBT and active controls (Cohen's d = 0.61; 0.27-0.97);p=.001) (Figure 6; Supplementary Appendix) (LoE A/RG 1).”

Psychodynamic therapy has not been evaluated against a waitlist condition.

“Psychodynamic (psychoanalytic) therapy (PdTh) has not been tested against a waitlist condition.”

A meta-analysis found a significant difference between CBT and active controls in SAD, with a small effect size (Cohen's d = 0.27; CI 0.10-0.43; p=.001).

“Our meta-analysis of studies with active controls showed a significant difference between CBT and active controls, however, the difference is small (Cohen's d = 0.27; CI 0.10-0.43;p=.001) (Figure 5; Supplementary Appendix) (LoE A/RG 1).”

Combining phenelzine with CBT was superior to either monotherapy.

“The combination of phenelzine with CBT was superior to both monotherapies.”

There is a lack of comparison studies.

“Comparison studies are lacking, except for one study showing superiority of CBT over fluoxetine.”

A separate meta-analysis reported that CBT was superior to active control conditions for children and adolescents with SAD.

“Also, another meta-analysis found that CBT for children and adolescents with SAD was superior to active control conditions (Yang et al. 2019).”

• cites Yang et al. 2019Not checked yet

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For fear of heights, virtual reality exposure therapy is superior to wait list.

“Virtual reality exposure therapy was superior to wait list; evidence that it is as effective as in vivo exposure is only based on one underpowered study (LoE D/RG 4).”

One study demonstrated that CBT was superior to fluoxetine.

“except for one study showing superiority of CBT over fluoxetine.”

One study showed CBT for selective mutism is superior to psychoeducation.

“It did not clearly separate from waitlist in the available studies; one study showed superiority to psychoeducation (LoE D/RG 3).”

In one study, cognitive behavioral therapy was less effective than medication for SAD.

“CBT was less effective than drug treatment in one study.”

Some studies found iCBT superior to waitlist.

“Some studies showed superiority over waitlist”

Internet-based cognitive behavioural therapy (iCBT) was found to be more effective than waitlist control in the majority of studies.

“Internet psychotherapeutic interventions based on CBT (iCBT) were superior to waitlist in most studies.”

For GAD and mixed anxiety disorders in children and adolescents, no clear superiority to non-specific control treatments could be determined.

“For GAD and mixed anxiety disorders in children and adolescents, no clear superiority to non-specific control treatments could be determined.”

In elderly patients with GAD, quetiapine was effective.

“Quetiapine was effective in elderly patients with GAD.”

In elderly patients with anxiety disorders, a study finding CBT equal to paroxetine was underpowered.

“A study showing that CBT was as effective as paroxetine was underpowered”

In children and adolescents with GAD, separation anxiety disorder, or mixed anxiety disorders, fluvoxamine showed efficacy in double-blind placebo-controlled studies.

“Fluvoxamine demonstrated efficacy in DBPC studies”

For panic disorder, desipramine and lofepramine were each effective in one double-blind placebo-controlled study.

“Desipramine and lofepramine were effective in one DBPC each”

In panic disorder, applied relaxation outperformed an active control, progressive muscle relaxation.

“AR was superior an active control, progressive muscle relaxation.”

In panic disorder, psychodynamic therapy was less effective than CBT.

“In comparison to CBT, it was less effective”

In the 14 years since the second version of this guideline, only a few new medications for these disorders have emerged.

“Regrettably, in the 14 years since the appearance of the second version of this guideline, only a few new medications for these disorders have emerged.”

In panic disorder, psychodynamic therapy was not tested against a waitlist condition.

“PdTh was not tested against a waitlist condition.”

In social anxiety disorder, a meta-analysis found a significant but small difference between CBT and active controls.

“A meta-analysis showed a significant difference between CBT and active controls; however, the difference is small.”

In social anxiety disorder, internet-based CBT was as effective as personal CBT.

“It was as effective as personal CBT.”

Anxiolytic treatment in patients with COPD and comorbid GAD or panic disorder may improve both physical and mental health.

“A review of studies of anxiolytic treatments in patients with chronic obstructive pulmonary disease (COPD) and comorbid GAD or panic disorder indicate that such treatment may improve both the physical and mental health (Mikkelsen et al. 2004).”

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A diagnosis of GAD incurred an odds ratio of 2.09 of a major cardiac event within a 2-year period.

“A diagnosis of GAD incurred an odds ratio of 2.09 of a major cardiac event within a 2year period (Frasure-Smith and Lesperance 2008).”

• cites Frasure-Smith and Lesperance 2008Not checked yet

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For specific phobias, one double-blind placebo-controlled study showed paroxetine efficacy.

“One DBPC study showed efficacy of paroxetine.”

In social anxiety disorder, only 2 of 14 comparisons of CBT with active controls showed a significant difference.

“However, of 14 comparisons with active control conditions, only 2 showed a significant difference.”

An anxiety factor based on four scales independently and prospectively predicted the incidence of myocardial infarction in older men.

“An anxiety factor based on four scales measuring psychasthenia, social introversion, phobia, and manifest anxiety independently and prospectively predicted the incidence of myocardial infarction in a study of older men (Shen et al. 2008).”

• cites Shen et al. 2008Not checked yet

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In children and adolescents with GAD, separation anxiety disorder, or mixed anxiety disorders, alprazolam was not superior to placebo in one study.

“Alprazolam was not superior to placebo in one study”

For specific phobias, paroxetine beat placebo in a small double-blind placebo-controlled study.

“Paroxetine was superior to placebo in a small DBPC study”

There is no evidence for negative effects of combining psychotherapy and pharmacotherapy.

“There is no evidence for negative effects of combining both treatments.”

For depressed patients with recent myocardial infarction or unstable angina, sertraline was found to be safe.

“For depressed patients with recent myocardial infarction or unstable angina, sertraline was found to be safe (Glassman et al. 2002).”

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Patients receiving CBT do show substantial improvement, as pre-post effect sizes of CBT are still large.

“This does not mean that patients receiving CBT do not show substantial improvement, as the pre-post effect sizes of CBT are still large (Bandelow et al. 2015).”

• cites Bandelow et al. 2015Not checked yet

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In one social anxiety disorder study, CBT was less effective than drug treatment.

“CBT was less effective than drug treatment in one study”

For fear of flying, virtual exposure outperformed waitlist and active controls.

“Virtual exposure was superior to waitlist and active controls”

In social anxiety disorder, CBT was more effective than waitlist conditions.

“CBT therapy for SAD was more effective than waitlist conditions.”

For specific phobias, one double-blind placebo-controlled study showed venlafaxine efficacy.

“One DBPC study showed efficacy of venlafaxine”

Evidence on combining CBT with drug treatment is inconclusive.

“Data on the combination of CBT and drug treatment are inconclusive.”

Every study of D-cycloserine for enhancing exposure or CBT effects was negative.

“All studies evaluating D-cycloserine for enhancing the effects of exposure or CBT were negative”

In elderly patients with GAD, pregabalin was effective.

“Pregabalin was effective in elderly patients with GAD.”

In social anxiety disorder, a meta-analysis comparing CBT with active controls found a medium effect size.

“Meta-analysis of studies comparing CBT with active controls revealed a medium effect size.”

In one social anxiety disorder study, CBT was more effective than fluoxetine.

“CBT was more effective than fluoxetine in one study.”

For panic disorder, a meta-analysis reported only a small difference between CBT and active controls.

“A metaanalysis found only a small difference between CBT and active controls.”

Evidence on applied relaxation for panic disorder is inconclusive.

“The evidence for AR is inconclusive.”

The guideline is based on evidence from randomised controlled trials.

“Adhering to the principles of evidence-based medicine, the present guideline is based on evidence from randomised controlled trials (RCTs).”

Treatment as usual is a very heterogeneous control condition, ranging from infrequent short visits to standard-quality psychological and/or pharmacological treatment.

“This is a very heterogenous control condition, as TAU can mean anything between infrequent and short visits to a mental health service and standard quality psychological and/or pharmacological treatment (Watts et al. 2015).”

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Comparisons with waitlist will usually show a significant difference between groups.

“Thus, comparisons with waitlist will mostly show a significant difference between the groups.”

When a psychotherapy is superior to pill placebo, this is a strong indicator of efficacy.

“When a psychotherapeutic method is superior to a pill placebo, this is a strong indicator for efficacy.”

Superiority of a psychotherapy to waitlist does not establish that it produces changes beyond nonspecific psychotherapy factors.

“If a form of psychotherapy was shown to be superior to waitlist, we still do not know whether this method would produce changes beyond any that might occur because of the nonspecific factors of psychotherapy, i.e. rapport, expectation of gain, and sympathetic attention (Seligman 1995).”

• cites Seligman 1995Not checked yet

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Many people who could benefit from anxiety treatment are neither diagnosed nor treated.

“However, many patients who might benefit from treatment are not diagnosed or treated (Alonso et al. 2018).”

• cites Alonso et al. 2018Not checked yet

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Results of comparisons with treatment as usual are difficult to interpret.

“Therefore, the results of comparisons with TAU are difficult to interpret.”

In the absence of early improvement, modifications in the treatment plan may be considered before 8-12 weeks.

“Altogether, these findings suggest that, in the absence of early improvement, modifications in the treatment plan may be considered before 8-12 weeks.”

Separation anxiety may not necessarily be caused by actual separation experiences in childhood.

“Separation anxiety may not necessarily be caused by actual separation experiences in childhood (Bandelow et al. 2001).”

• cites Bandelow et al. 2001Not checked yet

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In some patients, the measured pre-post effect is a combination of psychotherapy and medication.

“Thus, in some patients, the measured pre-post effect is in fact a combination of psychotherapy and medication in a substantial percentage of the participants.”

If partial response is seen after 4 weeks, the patient may still respond within the next 4-6 weeks of therapy.

“If partial response is seen after 4 weeks, it is still possible that the patient will respond within the next 4-6 weeks of therapy.”

Small studies are more prone to publication bias because journal editors may be reluctant to publish small studies showing no difference from a control group.

“Small studies are more prone to publication bias, as journal editors may be reluctant to publish small studies showing no difference to a control group.”

In GAD and SAD, a trial of at least 4 weeks is worthwhile before considering further intervention.

“Study data showed that in GAD and SAD, a trial of at least 4 weeks is worthwhile before considering further intervention (Baldwin et al. 2009).”

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Augmentation has the disadvantage that improvement after augmentation cannot be attributed to the second drug or the combination.

“this strategy has the disadvantage that should an improvement occur after augmentation, it is unclear whether it is due to the second drug or to the combination.”

Demonstrating psychotherapy efficacy at an expert site does not guarantee the same effect sizes in real-life conditions.

“Lastly, demonstrating efficacy of psychotherapy in a trial conducted at an expert site does not guarantee that the same effect sizes will be obtained in”

• cites Nutt and Sharpe 2008Not checked yet

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The longer a trial, the more its treatment effects could be attributable to spontaneous remission.

“The longer the trial, the more the treatment effects could be attributable to spontaneous remission.”

Some comparisons among SSRIs did not reveal differences in efficacy.

“Some comparisons among the SSRIs did not reveal differences with regard to efficacy (Bandelow et al. 2004;Perna et al. 2001), while escitalopram showed evidence of superiority over citalopram on some outcome measures (Bandelow et al. 2007).”

• cites Bandelow et al. 2004Not checked yet

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• cites Perna et al. 2001Not checked yet

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Long-lasting treatment effects in follow-up may be confounded by spontaneous remission or regression to the mean.

“Long-lasting treatment effects observed in the follow-up period may be confounded by effects of spontaneous remission or regression to the mean.”

One analysis did not find a difference in tolerability between SSRIs and imipramine.

“although one analysis did not find a difference in tolerability between SSRIs and imipramine (Otto et al. 2001).”

• cites Otto et al. 2001Not checked yet

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Drugs that show high efficacy in this meta-analysis and have a recommendation grade of 1 include escitalopram, paroxetine, and venlafaxine.

“Drugs that show high efficacy in this meta-analysis and have a recommendation grade of 1, included escitalopram, paroxetine, and venlafaxine.”

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Escitalopram showed evidence of superiority over citalopram on some outcome measures.

“Some comparisons among the SSRIs did not reveal differences with regard to efficacy (Bandelow et al. 2004;Perna et al. 2001), while escitalopram showed evidence of superiority over citalopram on some outcome measures (Bandelow et al. 2007).”

• cites Bandelow et al. 2007Not checked yet

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According to a meta-analysis, the effect sizes for SSRIs were higher than for the benzodiazepine alprazolam.

“According to a meta-analysis, the effect sizes for the SSRIs were higher than for the benzodiazepine alprazolam (Boyer 1995).”

• cites Boyer 1995Not checked yet

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The SSRIs citalopram, fluoxetine, paroxetine, and sertraline, the SNRI venlafaxine, the TCAs clomipramine and imipramine, and the benzodiazepine alprazolam have shown long-term efficacy in studies lasting 24 to 104 weeks.

“In summary, the SSRIs citalopram, fluoxetine, paroxetine, and sertraline, the SNRI venlafaxine, the TCAs clomipramine and imipramine, and the benzodiazepine alprazolam have shown longterm efficacy in these studies (see Table 5, Supplementary Appendix) which had a duration between 24 and 104 weeks.”

In a meta-analysis of all available studies for anxiety disorders, large differences were found between the various drugs.

“In a meta-analysis of all available studies for the treatment of anxiety disorders, pre-to-post effect sizes were used, making it possible to compare all medications with regard to their efficacy across the studies (Bandelow et al. 2015).In this study, large differences were found between the various drugs.”

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No differences could be found between alprazolam and imipramine in terms of global improvement.

“In a number of studies, alprazolam was compared with the tricyclic antidepressant imipramine (Andersch et al. 1991;Charney et al. 1986;CNCPS 1992;Lepola et al. 1990;Rizley et al. 1986;Taylor et al. 1990;Uhlenhuth et al. 1989).No differences could be found between the two drugs in terms of global improvement.”

• cites Andersch et al. 1991Not checked yet

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• cites Charney et al. 1986Not checked yet

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• cites CNCPS 1992Not checked yet

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In an open study, patients with panic disorder stabilized on imipramine who then received half their previous dose did not relapse or show sustained worsening.

“In an open study with the TCA imipramine, patients stabilized on imipramine who received further treatment with half their previous dose of imipramine did not show relapse or sustained worsening (Mavissakalian and Perel 1992).”

• cites Mavissakalian and Perel 1992Not checked yet

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In open comparisons, clonazepam was better tolerated than paroxetine in both short-term and long-term treatment.

“In open comparisons of clonazepam and paroxetine, clonazepam demonstrated a faster onset of action and greater clinical improvement than paroxetine, and in both short-term and long-term treatment, clonazepam was better tolerated (Freire et al. 2017;Nardi et al. 2012;Nardi et al. 2011).”

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• cites Nardi et al. 2012Not checked yet

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• cites Nardi et al. 2011Not checked yet

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In studies comparing TCAs and SSRIs, no differences in efficacy were found between the two classes.

“In studies comparing TCAs and SSRIs, no differences in terms of efficacy were found between the two classes of drugs (Amore et al. 1999;Bakish et al. 1996;Bakker et al. 1999a;Bystritsky et al. 1994;Cavaljuga et al. 2003;Lecrubier and Judge 1997;Wade et al. 1997), with the exception of the tetrayclic antidepressant maprotiline, which had no effect in contrast to fluvoxamine (Den Boer and Westenberg”

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• cites Bakish et al. 1996Not checked yet

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• cites Bakker et al. 1999aNot checked yet

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In patients with comorbid panic disorder and major depressive disorder, sertraline and imipramine were equally effective.

“Also, in patients with comorbid panic disorder and major depressive disorder, sertraline and imipramine were equally effective, but sertraline showed significantly greater tolerability and compliance than imipramine (Lepola et al. 2003).”

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In acute (short-term) treatment of panic disorder, SSRIs were associated with more adverse effects than benzodiazepines.

“Another meta-analysis found that in acute (short-term) treatment of panic disorder, SSRIs were associated with more adverse effects than benzodiazepines (Quagliato et al. 2019).”

• cites Quagliato et al. 2019Not checked yet

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The evidence for psychodynamic therapy is negative.

“However, as the evidence for psychodynamic therapy is negative, these results cannot be used as proof for the efficacy of CBT.”

• AssumptionRests on an assumption: For PDA, there are no comparisons of PdTh against waitlist.
• AssumptionRests on an assumption: In comparison to 'no treatment' or active controls, no differences were found for PdTh.
• AssumptionRests on an assumption: In one study, psychodynamic therapy was even less effective than the control treatment, relaxation.
• AssumptionRests on an assumption: In comparison to CBT, the majority of studies showed inferiority of PdTh.

In studies without a control condition, patients having residual symptoms despite being on an adequate dose of medication showed improvement after the introduction of CBT.

“In studies without control condition, patients having residual symptoms despite being on an adequate dose of medication showed improvement after the introduction of CBT (Heldt et al. 2003;Pollack et al. 1994).”

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• cites Pollack et al. 1994Not checked yet

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Most of these comparison studies were underpowered.

“Most trials that have compared psychotherapy (mostly CBT) and various medications did not find a difference; however, most of these studies were underpowered (Table 7; Supplementary Appendix).”

SAD requires long-term treatment.

“SAD is generally a persistent condition and requires long-term treatment.”

In comparison to medication, iCBT was less effective.

“According to a meta-analysis using pre-to post effect sizes, iCBT was marginally less effective than face-to-face CBT.In comparison to medication, iCBT was less effective (Bandelow and Wedekind 2022).”

• cites Bandelow and Wedekind 2022Not checked yet

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A previous meta-analysis has shown that CBT had an average pre-post effect size on the same level as pill placebos.

“A previous meta-analysis has shown that CBT is markedly less effective than medications in (Bandelow et al. 2015) and had an average pre-post effect size on the same level as pill placebos.”

• cites Bandelow et al. 2015Not checked yet

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Most trials that compared psychotherapy (mostly CBT) and various medications did not find a difference.

“Most trials that have compared psychotherapy (mostly CBT) and various medications did not find a difference; however, most of these studies were underpowered (Table 7; Supplementary Appendix).”

Follow-up studies of treatment effects are confounded because patients may receive other treatments outside the study protocol.

“The problem in follow-up studies is that the outcome is confounded by other treatments.”

• AssumptionRests on an assumption: In follow-up studies, patients who relapse often use treatments outside the study protocol and many resume the treatment that helped them during the study.
• AssumptionRests on an assumption: Long-lasting treatment effects seen in follow-up may be confounded by spontaneous remission or regression to the mean.

The results of studies comparing CBT with psychodynamic therapy cannot be used as proof for the efficacy of CBT.

“However, as the evidence for psychodynamic therapy is negative, these results cannot be used as proof for the efficacy of CBT.”

Evidence supporting psychodynamic therapy for GAD is weak.

“The evidence for PdTh is weak.”

Because the evidence is inconclusive, no recommendation can be made about combining medication and psychotherapy for GAD.

“Altogether, due to the lack of conclusive evidence, no recommendations regarding the combination of medications and psychotherapy can be given (LoE D/RG 4).”

SAD is generally a persistent condition.

“SAD is generally a persistent condition and requires long-term treatment.”

A meta-analysis which used pre-post effects found superiority of drug treatment over psychotherapy.

“A meta-analysis which used pre-post effects found superiority of drug treatment over psychotherapy (Bandelow et al. 2015).”

• cites Bandelow et al. 2015Not checked yet

  Not checked in the free run.

Psychodynamic therapy cannot be regarded as effective treatment.

“which itself cannot be regarded as effective treatment (LoE D/RG 4).”

A previous meta-analysis has shown that CBT is markedly less effective than medications.

“A previous meta-analysis has shown that CBT is markedly less effective than medications in (Bandelow et al. 2015) and had an average pre-post effect size on the same level as pill placebos.”

• cites Bandelow et al. 2015Not checked yet

  Not checked in the free run.

According to a meta-analysis using pre-to-post effect sizes, iCBT was marginally less effective than face-to-face CBT.

“According to a meta-analysis using pre-to post effect sizes, iCBT was marginally less effective than face-to-face CBT.In comparison to medication, iCBT was less effective (Bandelow and Wedekind 2022).”

• cites Bandelow and Wedekind 2022Not checked yet

  Not checked in the free run.

There is strong evidence for non-efficacy of psychodynamic therapy in PDA.

“Because of this strong evidence for non-efficacy, there is advice against the use of psychodynamic therapy in PDA (LoE A-/RG 1-).”

• AssumptionRests on an assumption: For PDA, there are no comparisons of PdTh against waitlist.
• AssumptionRests on an assumption: In comparison to 'no treatment' or active controls, no differences were found for PdTh.
• AssumptionRests on an assumption: In one study, psychodynamic therapy was even less effective than the control treatment, relaxation.
• AssumptionRests on an assumption: In comparison to CBT, the majority of studies showed inferiority of PdTh.

In that study, the difference between clonazepam augmentation and placebo was not statistically significant.

“While there was a numerical advantage for the addition of clonazepam relative to a switch to venlafaxine or continuation on sertraline (plus placebo), the difference between clonazepam and placebo augmentation was not statistically significant, nor was the difference between venlafaxine and sertraline plus placebo (Pollack et al. 2014).”