Antidepressants Are Effective in Decreasing Neuropathic Pain After SCI: A Meta-Analysis

Objective:

To systematically review and assess the effectiveness and safety of antidepressants for neuropathic pain among individuals with spinal cord injury (SCI).

Methods:

A systematic search was conducted using multiple databases for relevant articles published from 1980 to April 2014. Randomized controlled trials (RCTs) involving antidepressant treatment of neuropathic pain with ≥3 individuals and ≥50% of study population with SCI were included. Two independent reviewers selected studies based on inclusion criteria and then extracted data. Pooled analysis using Cohen’s d to calculate standardized mean difference, standard error, and 95% confidence interval for primary (pain) and other secondary outcomes was conducted.

Results:

Four RCTs met inclusion criteria. Of these, 2 studies assessed amitriptyline, 1 trazadone, and 1 duloxetine among individuals with neuropathic SCI pain. A small effect was seen in the effectiveness of antidepressants in decreasing pain among individuals with SCI (standardized mean difference = 0.34 ± 0.15; 95% CI, 0.05-0.62; P = .02). A number needed to treat of 3.4 for 30% or more pain relief was found by pooling 2 studies. Of these, significantly higher risk of experiencing constipation (risk ratio [RR] = 1.74; 95% CI, 1.09-2.78; P = .02) and dry mouth (RR = 1.39; 95% CI, 1.04-1.85; P = .02) was found amongst individuals receiving antidepressant treatment compared to those in the control group.

Conclusion:

The current meta-analysis demonstrates that antidepressants are effective in reducing neuropathic SCI pain. However, this should be interpreted with caution due to the limited number of studies. Further evaluation of long-term therapeutic options may be required.     

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.     

Practical aspects of telehealth: doctor–patient relationship and communication

The fourth in a series of articles about the practical aspects of telehealth, this paper provides advice and information for specialists to communicate effectively with patients during a telehealth video consultation.     

Successful treatment of macrophage activation syndrome complicating adult Still disease with anakinra

A previously healthy 20‐year‐old man presented with adult Still disease (ASD). He developed life‐threatening macrophage activation syndrome (MAS), which was refractory to standard immunosuppression but responded dramatically to the IL‐1 receptor antagonist anakinra. Subsequent immunological investigations included assessment of the perforin expression of natural killer (NK) cells and CD8+ T cells, which confirmed MAS.     

Neuropathic Pain Post Spinal Cord Injury Part 2: Systematic Review of Dorsal Root Entry Zone Procedure

Background:

Pharmacotherapy may not sufficiently reduce neuropathic pain in many individuals post spinal cord injury (SCI). The use of alternative therapies such as surgery may be effective in reducing neuropathic pain in these individuals. However, because of the invasive nature of surgery, it is important to examine the evidence for use of this treatment.

Objective:

The purpose of this study was to conduct a systematic review of published literature on the surgical treatment of neuropathic pain after SCI.

Methods:

MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for articles in which surgical treatment of pain after SCI was examined. Articles were restricted to the English language. Article selection was conducted by 2 independent reviewers with the following inclusion criteria: the subjects participated in a surgical intervention for neuropathic pain; at least 50% of the subjects had an SCI; at least 3 subjects had an SCI; and a definable intervention involving the dorsal root entry zone (DREZ) procedure was used to reduce pain. Data extracted included study design, study type, subject demographics, inclusion and exclusion criteria, sample size, outcome measures, and study results. Randomized controlled trials (RCTs) were assessed for quality using the Physiotherapy Evidence Database (PEDro) assessment scale. Levels of evidence were assigned to each intervention using a modified Sackett scale.

Results:

Eleven studies met the inclusion criteria. One study provided level 2 evidence, and the rest provided level 4 evidence. The DREZ procedure was shown to be more effective for segmental pain than for diffuse pain after SCI. Further, individuals with conus medullaris level injury were found to have a higher level of neuropathic pain relief than those with cervical, thoracic, or cauda equina injury.

Conclusions:

The studies demonstrated that the DREZ procedure may be effective in reducing segmental pain. Hence, DREZ may be important in treatment of neuropathic pain in individuals resistant to less invasive treatments. Because the studies lacked control conditions and examination of long-term effects, there is a need for larger trials with more stringent conditions.Key words: pain, spinal cord injury, surgical treatmentPain is a major cause of distress and disability in persons with spinal cord injury (SCI). It has been shown to lead to social isolation, unemployment, decreased function, decreased quality of life, depression, and even suicide.^1,2 More than 77% of individuals with an SCI indicated that pain interfered with one or more of their daily activities including sleep (40%), exercise (34.9%), and work (33.6%).² The International Association for the Study of Pain (IASP) defines neuropathic pain as “pain caused by a lesion or disease of the somatosensory nervous system.”³ After an SCI, individuals often report the onset of chronic neuropathic pain caudal to the level of the lesion or at the same level within the associated spinal cord segment.⁴ Dijkers et al⁵ reported no difference in the prevalence of pain based on level or completeness.The reported incidence of neuropathic pain after SCI varies greatly among studies, but between 10% and 30% of patients with SCI experience pain severe enough to interfere with their activities of daily living^6,7 and may require surgical intervention to relieve persistent and refractory pain.^4,8 Unmanageable neuropathic pain occurs more often in individuals with conus medullaris and cauda equina lesions where damage also involves the peripheral nerve roots.⁸When pharmacological and other noninvasive treatments fail to reduce pain, surgical spinal cord stimulation and dorsal root entry zone (DREZ) ablation treatments, such as DREZ lesioning and microsurgical DREZotomy (MDT), can be considered as options for the management of refractory pain.⁹ Neurosurgical procedures to reduce neuropathic pain should be reserved for cases in which medical therapies have failed to sufficiently reduce pain.⁴ The risks associated with ablative surgeries can be significant for individuals with incomplete neurological deficits; therefore, DREZ ablation is generally only considered a treatment option when neuropathic pain is present after a complete SCI.⁸ The MDT procedure targets for ablation the nociceptive fibers in the lateral bundle of the dorsal rootlet, the deafferented neurons of the dorsal horn, and the medial portion of the Lissauer tract.^4,6 This systematic review was conducted to assess the effectiveness of DREZ ablation therapies in reducing neuropathic pain in individuals following SCI.