Clinical practice for unspecified anxiety disorder in primary care

Abstract Aim Clinicians face difficulties in making treatment decisions for unspecified anxiety disorder due to the absence of any treatment guidelines. The objective of this study was to investigate how familiar and how often primary care physicians use pharmacological and nonpharmacological approaches to manage the disorder. Methods A survey was conducted among 117 primary care physicians in Japan who were asked to assess the familiarity of using each treatment option for unspecified anxiety disorder on a binary response scale (0 = “unfamiliar,” 1 = “familiar”) and the frequency on a nine‐point Likert scale (1 = “never used,” 9 = “frequently used”). Results While several benzodiazepine anxiolytics were familiar to primary care physicians, the frequencies of prescribing them, including alprazolam (4.6 ± 2.6), ethyl loflazepate (3.6 ± 2.4), and clotiazepam (3.5 ± 2.3), were low. In contrast, certain nonpharmacological options, including lifestyle changes (5.4 ± 2.3), coping strategies (5.1 ± 2.7), and psychoeducation for anxiety (5.1 ± 2.7), were more commonly utilized, but to a modest extent. When a benzodiazepine anxiolytic drug failed to be effective, primary care physicians selected the following management strategies to a relatively high degree: differential diagnosis (6.4 ± 2.4), referral to a specialist hospital (5.9 ± 2.5), lifestyle changes (5.2 ± 2.5), and switching to selective serotonin reuptake inhibitor (5.1 ± 2.4). Conclusion Primary care physicians exercise caution when prescribing benzodiazepine anxiolytics for unspecified anxiety disorder. Nonpharmacological interventions and switching to SSRI are modestly employed as primary treatment options and alternatives to benzodiazepine anxiolytics. To ensure the safe and effective treatment of unspecified anxiety disorder in primary care, more information should be provided from field experts.


INTRODUCTION
2][3] It affects a broad spectrum of individuals, ranging from those with subthreshold symptoms, which are more commonly reported than diagnosable disorders, 4,5 to those with specific diagnoses, including generalized anxiety disorder, panic disorder, and social anxiety disorder.
Furthermore, there are individuals with unspecified anxiety disorder, characterized by significant anxiety or phobias that do not meet the specific criteria for other anxiety disorders.A cross-sectional study based on nationally representative data for physician office-based visits in the United States demonstrated that unspecified anxiety disorder was the primary diagnosis among anxiety disorders, increasing from 50% between 1999 and 2002 to 62% between 2007 and 2010. 6imary care is often the preferred option for individuals seeking treatment for anxiety compared to specialty mental health settings. 7,8wever, anxiety is frequently undertreated in primary care, leading to patients receiving inadequate pharmacological or psychological treatment, or sometimes no treatment at all. 9,10In addition, there is currently a lack of information available on practical management strategies for unspecified anxiety disorder in real-world settings.The absence of treatment guidelines for this disorder presents a challenge for clinicians in making treatment decisions.The aim of the present study was therefore to investigate the primary care physicians' familiarity and frequency of using pharmacological and nonpharmacological strategies for managing unspecified anxiety disorder.

METHODS
The task force comprised 13 mental health professionals and primary care providers who identified eight clinical questions concerning the management of unspecified anxiety disorder.For each of these questions, available treatment options were organized according to established treatment guidelines for other anxiety disorders [11][12][13][14] and clinical practice.Invitations were extended via email to primary care physicians who were affiliated with the Japan Primary Care Association to partake in a questionnaire survey from June 29, 2022, to July 31, 2022.This society has a board certification system in which about 11% of the members have been certified as specialists in this field.Those who provided their consent were asked to assess each treatment option based on two criteria: first, the familiarity with each option on a binary response scale (0 = "unfamiliar," 1 = "familiar"), and, second, the frequency on a nine-point Likert scale (1 = "never used," 9 = "frequently used").As the options presented in Q5 and Q6 (Table S1) are common, the question regarding familiarity was excluded from these particular questions.The questionnaire included the definition of unspecified anxiety disorder as outlined in the DSM-5 in their native language (i.e., Japanese).The clinical questions and treatment options are presented in Table S1

Participant characteristics
Adequate participation was achieved, with 117 primary care physicians (i.e., members of the Japan Primary Care Association) completing the questionnaire.The mean age of respondents was 47.2 ± 10.3 years.The proportions of male and female respondents were 76.1% and 18.8%, respectively, while 5.1% opted not to provide this information.

Management when a benzodiazepine anxiolytic drug is ineffective
When a benzodiazepine anxiolytic drug failed to improve anxious symptoms, several alternative strategies were known to over 80% of the respondents, including switching to a selective serotonin reuptake inhibitor (SSRI) (94.9%), a serotonin and norepinephrine reuptake inhibitor (SNRI) (93.2%), or another benzodiazepine anxiolytic drug (92.3%) and increasing the dose of an anxiolytic drug (92.3%).Among these, the most frequently used options included switching to an SSRI (5.1 ± 2.4), mirtazapine (4.3 ± 2.6), and an SNRI (4.1 ± 2.5) (Table 2).In terms of nonpharmacological management, more than 80% of the primary care physicians were aware of multiple choices, including differential diagnosis (99.1%), referral to a specialist hospital (97.4%), lifestyle changes (94.0%), coping strategies (90.6%), and psychoeducation for anxiety (86.3%).Similarly to primary management, the frequencies of using some nonpharmacological managements, including differential diagnosis (6.4 ± 2.4), referral to a specialist hospital (5.9 ± 2.5), and lifestyle changes (5.2 ± 2.5), were numerically higher than those of any pharmacological strategies, but to a modest extent,.

Discontinuation of benzodiazepine anxiolytic drugs
The ratings for all possible options for tapering or discontinuing a benzodiazepine anxiolytic drug following the improvement of anxious symptoms ranged from 3.4 ± 2.3 for the option "immediately after improvement" to 4.6 ± 2.4 for the option "after 1-3 month(s)." Reasons that were deemed acceptable for continuing a benzodiazepine anxiolytic drug included a history of relapsed anxious symptoms (6.3 ± 2.1), anticipation of physical or mental deterioration (6.3 ± 2.1), and patient desire (6.2 ± 2.2).Various strategies were found to be familiar and modestly used when tapering or discontinuing benzodiazepine anxiolytic drugs, including gradual reduction (100.0%and 6.7 ± 2.1, respectively), switching to pro re nata (PRN) (95.7% and 5.4 ± 2.5, respectively), self-management (94.9% and 4.7 ± 2.4, respectively), and switching to another benzodiazepine anxiolytic T A B L E 1 Primary treatment strategy for unspecified anxiety disorder with more than 80% familiarity.T A B L E 2 Treatment strategy for unspecified anxiety disorder when a benzodiazepine anxiolytic drug fails to improve anxious symptoms with more than 80% familiarity.

Note:
The options are listed in the order of the mean values of the frequency.

DISCUSSION
The present study provides insight into the practical management approaches used by primary care physicians for unspecified anxiety disorder.Our findings indicate that primary care physicians exercise caution when prescribing benzodiazepine anxiolytic drugs and resort to alternative management strategies, including fundamental nonpharmacological interventions, to some extent for this condition.This is consistent with expert consensus that benzodiazepine anxiolytics are not recommended as first-line treatment for unspecified anxiety disorder. 15spite the familiarity, benzodiazepine anxiolytics were not highly prioritized as primary treatment for unspecified anxiety disorder.There was no consistent pattern observed in the duration of action among the familiar and relatively prescribed benzodiazepine anxiolytics for primary treatment.In cases where benzodiazepine anxiolytics were prescribed, physicians tended to discontinue them within a relatively short period once the anxious symptoms improved, unless there were justifiable reasons to continue their use.This is likely because the continuous use of benzodiazepines is associated with various adverse events such as sedation, cognitive impairments, and dependence. 16While recent reports indicate that their safety could also be maintained in the long term, 17-19 primary care physicians may limit their use to specified anxiety disorders, including generalized anxiety disorder, panic disorder, and social anxiety disorder, for which benzodiazepine anxiolytics have shown some efficacy. 11,14On a different front, there may be some possibility that the respondents of the questionnaire (i.e., members of the Japan Primary Care Association) have better knowledge than general primary care physicians in the treatment of anxiety and the complications associated with benzodiazepines.Considering the prescription rate for anxiolytics in the general population of Japan has remained steady at approximately 2% since 2009, 20 benzodiazepine anxiolytics may be more commonly utilized for unspecified anxiety disorders in general medical practice than presently reported.
Primary care physicians evaluated fundamental nonpharmacological treatments over benzodiazepine anxiolytics as the initial line of treatment for unspecified anxiety disorder.2][23][24] It is noteworthy that the respondents of the questionnaire are provided with training on basic nonpharmacological treatments for mental disorders at academic conferences and seminars.Moreover, the specialists of this society are certified based on written examinations, practical examinations, oral examinations, and portfolio evaluations on common clinical practice, including fundamental nonpharmacological interventions and brief psychotherapy for anxiety disorders.However, the frequency to use these strategies was often modest in the present survey, rated 5.4 or less points on a 9-point scale.Additionally, referral to a specialist hospital followed differential diagnosis as the management primary care physicians conducted when benzodiazepine anxiolytics failed to improve anxious symptoms.To enhance the implementation of these interventions, it is suggested that primary care physicians may need more information from field experts, along with standardized resources, support, and educational programs to alleviate their burden.
When a benzodiazepine anxiolytic drug was ineffective, primary care physicians endorsed switching to an SSRI as a pharmacological alternative at a similar level to nonpharmacological strategies.On tapering or discontinuing a benzodiazepine anxiolytic drug, various pharmacological strategies were employed, including gradual reduction, switching to a PRN, and switching to an SSRI, which were given more preference compared to fundamental nonpharmacological managements.However, the ratings for the frequencies of these treatments were also not high except for gradual reduction, which was rated 6.7 point on a 9-point scale.These findings indicate that primary care physicians are knowledgeable about alternative benzodiazepine treatments, but not very practiced.It is worth noting that the efficacy of facilitating benzodiazepine discontinuation in chronic benzodiazepine users has only been systematically examined for paroxetine among SSRIs and that there was no significant difference in benzodiazepine T A B L E 3 Treatment strategy for tapering or discontinuing a benzodiazepine anxiolytic drug in unspecified anxiety disorder with more than 80% familiarity.discontinuation at the end of intervention between paroxetine and placebo or no intervention. 25This lack of evidence should be taken into consideration when determining treatment strategies.
The present study has several limitations that should be considered when interpreting the results.First, the results were based solely on responses to questionnaire surveys completed by primary care physicians, which may not fully reflect actual therapy practices.
Second, the lack of adequate information provided for certain clinical questions may have hindered respondents' ability to select appropriate treatment options.The clinical questions concerning alternative interventions of benzodiazepine anxiolytics did not account for the duration of action of these medications.Third, the question used to assess primary strategies for unspecified anxiety disorder did not consider pharmacological treatments other than benzodiazepine anxiolytics.Fourth, the generalizability of our findings may be limited to the Japanese medical community.Finally, the questionnaire survey was conducted exclusively among primary care physicians who were affiliated with the Japan Primary Care Association.Additionally, the proportion of certified specialists from this society among the participants of the present survey were not inquired.
In conclusion, our findings indicate that benzodiazepine anxiolytics are not the primary treatment option for unspecified anxiety disorder according to primary care physicians, despite their familiarity.They are only prescribed for short periods after symptom improvement, if deemed necessary.Fundamental nonpharmacological interventions and switching to SSRIs are preferred for primary treatment and as alternatives to benzodiazepine anxiolytics although the frequencies to use these choices are modest.As unspecified anxiety disorder is often treated in primary care, it is recommended that field experts provide primary care physicians with more information and support to ensure proper treatment for this condition.

AUTHOR CONTRIBUTIONS
Acquisition and data analysis, drafting the manuscript: Hitoshi Sakurai.
. The completion of the survey took approximately 15 min.Participation in the survey by the experts was voluntary and without any incentives.Respondents were also asked to indicate their age and gender.The rate of familiarity and the mean value and standard deviation of frequency were calculated for each treatment option.This study was approved by the institutional review board of St. Luke's International University (2021-604).
The options are listed in the order of the mean values of the frequency.