Ministry of Health Clinical Practice Guidelines: Anxiety Disorders

The Ministry of Health (MOH) has developed the clinical practice guidelines on Anxiety Disorders to provide doctors and patients in Singapore with evidence-based treatment for anxiety disorders. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on anxiety disorders, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

1.1 Background information

Anxiety disorders are known to be one of the most prevalent of psychiatric conditions, yet they often remain under-diagnosed and under-treated. Their chronic, disabling symptoms cause considerable burden not only to sufferers but also to their families, and contribute to poorer quality of life and considerable economic burden on society.In many instances, there is a delay in seeking treatment and in some cases such delay may stretch up to nearly ten years. This may result from ignorance of the condition, fear of taking medications, and the stigma of receiving a psychiatric diagnosis, and or having to accept psychiatric treatment.The anxiety disorders include panic disorder with or without agoraphobia, social anxiety disorder, specific phobia, obsessive-compulsive disorder, generalised anxiety disorder, acute stress disorder and post-traumatic stress disorder. In the clinical evaluation of anxiety disorders, it is important to ascertain the type of anxiety disorder present. This would allow treatment to be targeted at the specific type of disorder.These guidelines are developed to provide practical, evidence-based recommendations to primary care physicians and specialists in psychiatry for the diagnosis and management of the anxiety disorders.The first edition of the guidelines was published in 2003. In this edition, we present data from newer research as well as older data not previously reported in the earlier guidelines.For example, we examine the efficacy of combining medications with psychological therapy over medications alone, or psychological therapy alone. In view of the majority of anxiety sufferers being female we have made recommendations for pharmacotherapy during pregnancy and breastfeeding. As these guidelines are intended for use in the Singapore context, we have omitted treatments that are currently not available in Singapore.

1.2 Aim

These guidelines are developed to facilitate the diagnosis and assessment of the anxiety disorders, and to ensure that their management is appropriate and effective.

1.3 Scope

These guidelines will cover the management of anxiety disorders in adults and address the issues of medication use during pregnancy and breastfeeding.

1.4 Target group

The content of the guidelines will be useful for all doctors treating patients with anxiety disorders. Efforts have been made to ensure that the guidelines are particularly useful for primary care physicians and specialists in psychiatry, including all those involved in the assessment and management of patients with anxiety disorders in the community. The doctor treating the patient is ultimately responsible for clinical decisions made after reviewing the individual patient’s history, clinical presentation and treatment options available.

1.5 Development of guidelines

These guidelines have been produced by a committee of psychiatrists, a clinical psychologist, pharmacist, patient representative, and family practitioners appointed by the Ministry of Health. They were developed by revising the existing guidelines, reviewing relevant literature, including overseas clinical practice guidelines, and by expert clinical consensus of professionals with experience in treating patients in the local setting.The following principles underlie the development of these guidelines:

• Treatment recommendations are supported by scientific evidence whenever possible (randomised controlled clinical trials represent the highest level of evidence) and expert clinical consensus is used when such data are lacking.
• Treatment should maximise therapeutic benefits and minimise side effects.

1.6 What’s new in the revised guidelines

This edition of the guidelines contains updated recommendations based on latest evidence, as well as detailed discussions and recommendations on the management of anxiety disorders in adult populations.The following represent changes to the revised guidelines

• An extensive review of the literature, including new evidence. This involved the re-writing and extensive revision of the chapters.
• Length of treatment, which provides answers to a pertinent question.
• Use of medications during pregnancy and breastfeeding. Given that females are more likely to be at risk of being diagnosed with anxiety disorders, this is an important subject.

We are aware that the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) was released in 2013. In DSM-5, post-traumatic stress disorder and obsessive-compulsive disorder have been removed and classified separately from the rest of the anxiety disorders. If we were to adhere strictly to DSM-5, this would entail omitting discussion on post-traumatic stress disorder and obsessive-compulsive disorder. As it is our aim to provide an update on the 2003 guidelines, post-traumatic stress disorder and obsessive-compulsive disorder have been included in this edition of the guidelines.In addition, anxiety conditions in children are included in DSM-5. Since the present guidelines are meant to address only adult anxiety disorders, guidelines on children’s anxiety conditions are not included here.Hence, for purposes of these guidelines, we will continue to use classifications based on the International Classification of Diseases-10 (ICD-10) and DSM-IV-TR criteria.

1.7 Review of guidelines

Evidence-based clinical practice guidelines are only as current as the evidence that supports them. Users must keep in mind that new evidence could supersede recommendations in these guidelines. The workgroup advises that these guidelines be scheduled for review five years after publication, or when new evidence appears that requires substantive changes to the present recommendations.     

Unmanipulated Reduced-Intensity Stem Cell Transplantation from a Haploidentical Donor Mismatched at 3 HLA Antigens to a Patient with Leukemic Transformation of Myelodysplastic Syndrome: Successful Second Transplantation after Graft Rejection

We present the case of a patient with myelodysplastic syndrome who experienced leukemia transformation and subsequently underwent transplantation of unmanipulated peripheral blood stem cells from a haploidentical sibling mismatched at 3 HLA antigens, along with a reduced-intensity regimen (fludarabine, busulfan, and anti-T-lymphocyte globulin) and tacrolimus-containing graft-versus-host disease (GVHD) prophylaxis. The patient experienced graft rejection but successfully underwent a second transplantation from the same donor with a slightly intensified conditioning regimen. Although the patient developed life-threatening cytomegalovirus (CMV) pneumonia following the second transplantation, he recovered completely from the pneumonia with intensive supportive therapy. He is still in complete remission past day 1000 in the absence of GVHD. As far as we know, this report is the first to describe a successful second transplantation that was performed for graft rejection following HLA-haploidentical nonmyeloablative stem cell transplantation. Furthermore, we emphasize that patients should be carefully monitored for CMV infection when reduced-intensity conditioning is given repeatedly over a short period.     

Effect of combined intracoronary adenosine and nicorandil on no-reflow phenomenon during percutaneous coronary intervention.

BACKGROUND: This study aimed to clarify the effect of intracoronary administration of combined adenosine and nicorandil on the no-reflow phenomenon. METHODS AND RESULTS: Fifty patients (67+/-10 years, 30 male) with acute myocardial infarction (AMI) who developed no-reflow phenomenon during primary percutaneous coronary intervention (PCI) between June 2001 and May 2003 comprised the study group, which was divided into 2 groups: group I [25 patients, 67+/-10 years, 13 male; adenosine (24 microg/ml) alone in addition to nitrate] and group II [25 patients, 66+/-9 years, 17 male; combined intracoronary administration of adenosine and nicorandil (2 mg/ml) in addition to nitrate]. In-hospital and 6-month major adverse cardiac events (MACE) after PCI were compared between the 2 groups. Risk factors of coronary disease, left ventricular ejection fraction and wall motion score were not significantly different between the 2 groups (p=NS). Time interval from the onset of chest pain to PCI, number of involved vessels, lesion type according to ACC/AHA classification and TIMI flow grade (TFG) were not significantly different in both groups (p=NS). Incidence of thrombosis or dissection after balloon angioplasty, diameter and length of stent, and use of Reopro during PCI were not significantly different. TFG after PCI (2.0+/-0.9 vs 2.6+/-0.6, p=0.024), DeltaTFG (1.5+/-1.1 vs 2.2+/-1.0, p=0.033) and difference in TIMI frame count (TFC) before and after PCI (DeltaTFC) were greater in group II than group I (45.2+/-24.5 vs 63.6+/-23.2, p=0.014). Myocardial blush score 3 was obtained more frequently in group II than group I (44% vs 76%, p=0.014). In-hospital death did not occur in any of group II, but 4 patients of group I died (p=0.043). Two cases of MACE developed in each group and heart failure occurred in 3 (12%) of group I and 1 (4%) of group II patients during the 6-month follow-up (p=NS). CONCLUSIONS: Intracoronary administration of adenosine combined with nicorandil may improve both the occurrence of no-reflow in patients during PCI for AMI and short-term clinical outcome, compared with adenosine alone.     

Efficacy of directional coronary atherectomy before stent implantation for coronary ostial lesions

We evaluated stent implantation following directional coronary atherectomy (DCA) for coronary ostial lesions. The subjects were 27 patients (27 lesions) who underwent stent deployment after DCA, and 47 patients (47 lesions) who underwent stent deployment alone as the control group. There were no differences in numbers of lesions with multi-vessel disease, left anterior descending artery lesions, de novo lesions or reference vessel diameters in the two groups. The percent diameter stenosis after stent implantation was lower in the DCA-stent group than in the stent-alone group (9 +/- 10% versus 17 +/- 14%, respectively; p < 0.01). The initial procedural success rate was 92.6% in the DCA-stent group and 91.4% in the stent-alone group. The initial clinical success rate was 100% in the DCA-stent group and 95.7% in the stent-alone group. The restenosis rate was lower in the DCA-stent group (20% versus 43% in the stent-alone group). This study showed that debulking by DCA before stenting is more effective compared to stenting alone.     

Role of substance P in suppressing growth hormone release in the rat.

To evaluate a possible physiological role of endogenous substance P (SP) in the control of growth hormone (GH; somatotropin) secretion, a specific antiserum against SP (anti-SP) was injected intraventricularly (3 microliters into the third cerebral ventricle) in unanesthetized unrestrained normal male rats. Control rats received an equivalent volume of normal rabbit serum (NRS). Intraventricular injection of the NRS lowered plasma GH concentrations significantly. The lowering was detected on first measurement at 10 min after injection and was maximal at 30 min. This was followed by a return toward the initial levels. Third ventricular injection of antiserum significantly increased plasma GH in comparison with control animals injected with NRS. The effect was observed within 10-20 min, and levels remained elevated for the 120-min duration of the experiment. To confirm the possible inhibitory role of endogenous SP on GH release, 3 microliters of 0.9% NaCl (saline) alone or saline containing a specific antagonist of SP, [D-Pro2,D-Trp7,9]SP, was injected into the third ventricle of normal male rats. The antagonist also increased plasma GH significantly (P less than 0.005) within 5 min compared with values in the saline-injected control group. Levels remained elevated for 30 min but had returned toward control values 60 min after injection. In contrast, synthetic SP significantly decreased plasma GH when injected intravenously or intraventricularly compared with plasma GH in the control saline-injected group. To investigate a possible direct action of SP on GH release from the anterior pituitary gland, we incubated synthetic SP with dispersed anterior pituitary cells for 1 hr. The release of GH from incubated anterior pituitary cells was not affected at any dose of SP (10(-9) to 10(-6) M) tested. These data strongly indicate that endogenous SP has a physiological inhibitory role in the control of GH secretion at the level of the hypothalamus in the male rat.     

Prevalence of Gastroesophageal Reflux Disease Symptoms and Uninvestigated Dyspepsia in Korea: A Population-Based Study

Various reports on the prevalence of gastroesophageal reflux disease (GERD) and uninvestigated dyspepsia have been conducted in Western countries. We sought to determine the frequency of GERD symptoms and uninvestigated dyspepsia in Korea. Telephone interviews were conducted with 1,044 individuals. Of all subjects, 7.1% reported that GERD symptoms were present at least once a week, and 3.8% at least twice a week. The prevalence of heartburn according to educational level and acid regurgitation according to age was significantly different (P < 0.05). The prevalence of uninvestigated dyspepsia was reported as 12.2%. Dyspepsia was divided into subgroups of 34% ulcer-like, 56% dysmotility-like, and 10% nonspecific. The occurrence of dyspepsia did not vary according to age, gender, educational level and household income. As frequency of GERD symptoms increased, quality of life significantly decreased. We concluded that GERD symptoms and uninvestigated dyspepsia were prevalent in Korea. The prevalence was similar to that of other Asian countries.