Long term evaluation of a multidisciplinary trigeminal neuralgia service.

BACKGROUND: Trigeminal neuralgia is an episodic severe neuralgic pain and can be managed both medically and surgically. If possible, this should be directed by a Multidisciplinary Team (MDT) of specialised surgeons, physicians, dentists, psychologists and specialist nurses with access to all treatment modalities, which enables patients to make an informed decision about their future management. OBJECTIVE: The aim of this study was to review the outcomes of patients managed by an MDT clinic, in a single institute over an eleven-year period. METHODS: A prospective database was used to identify patients with trigeminal neuralgia or its variants who had attended a joint MDT clinic. The electronic notes were examined for demographics, onset and duration of trigeminal neuralgia, medications history, pain scores and details of surgical procedures if any by two independent assessors. RESULTS: Three hundred thirty-four patients attended the MDT between 2008-2019. Forty-nine of them had surgery before being referred to the service and were included but analysed as a subgroup. Of the remaining patients, 54% opted to have surgery following the MDT either immediately or at a later date. At the last reported visit 55% of patients who opted to have surgery were pain free and off medications, compared to 15.5% of medically managed patients. Surgical complications were mostly attributable to numbness and in the majority of cases this was temporary. All patients who were not pain free, had complications after surgery or opted to remain on medical therapy were followed up in a facial pain clinic which has access to pain physicians, clinical nurse specialists and a tailored pain management program. Regular patient related outcome measures are collected to evaluate outcomes. CONCLUSION: An MDT clinic offers an opportunity for shared decision making with patients deciding on their personal care pathway which is valued by patients. Not all patients opt for surgery, and some continue to attend a multidisciplinary follow up program. Providing a full range of services including psychological support, improves outcomes.

Interventions for treating burning mouth syndrome.

BACKGROUND: Burning mouth syndrome (BMS) is a term used for oral mucosal pain (burning pain or discomfort in the tongue, lips or entire oral cavity) without identifiable cause. General population prevalence varies from 0.1% to 3.9%. Many BMS patients indicate anxiety, depression, personality disorders and impaired quality of life (QoL). This review updates the previous versions published in 2000 and 2005. OBJECTIVES: To determine the effectiveness and safety of any intervention versus placebo for symptom relief and changes in QoL, taste, and feeling of dryness in people with BMS. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 31 December 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11) in the Cochrane Library (searched 31 December 2015), MEDLINE Ovid (1946 to 31 December 2015), and Embase Ovid (1980 to 31 December 2015). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. We placed no restrictions on the language or date of publication when searching the electronic databases SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any treatment against placebo in people with BMS. The primary outcomes were symptom relief (pain/burning) and change in QoL. Secondary outcomes included change in taste, feeling of dryness, and adverse effects. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Outcome data were analysed as short-term (up to three months) or long-term (three to six months). MAIN RESULTS: We included 23 RCTs (1121 analysed participants; 83% female). Interventions were categorised as: antidepressants and antipsychotics, anticonvulsants, benzodiazepines, cholinergics, dietary supplements, electromagnetic radiation, physical barriers, psychological therapies, and topical treatments.Only one RCT was assessed at low risk of bias overall, four RCTs' risk of bias was unclear, and 18 studies were at high risk of bias. Overall quality of the evidence for effectiveness was very low for all interventions and all outcomes.Twenty-one RCTs assessed short-term symptom relief. There is very low-quality evidence of benefit from electromagnetic radiation (one RCT, 58 participants), topical benzodiazepines (two RCTs, 111 participants), physical barriers (one RCT, 50 participants), and anticonvulsants (one RCT, 100 participants). We found insufficient/contradictory evidence regarding the effectiveness of antidepressants, cholinergics, systemic benzodiazepines, dietary supplements or topical treatments. No RCT assessing psychological therapies evaluated short-term symptom relief.Four studies assessed long-term symptom relief. There is very low-quality evidence of a benefit from psychological therapies (one RCT, 30 participants), capsaicin oral rinse (topical treatment) (one RCT, 18 participants), and topical benzodiazepines (one RCT, 66 participants). We found no evidence of a difference for dietary supplements or lactoperoxidase oral rinse. No studies assessing antidepressants, anticonvulsants, cholinergics, electromagnetic radiation or physical barriers evaluated long-term symptom relief.Short-term change in QoL was assessed by seven studies (none long-term).The quality of evidence was very low. A benefit was found for electromagnetic radiation (one RCT, 58 participants), however findings were inconclusive for antidepressants, benzodiazepines, dietary supplements and physical barriers.Secondary outcomes (change in taste and feeling of dryness) were only assessed short-term, and the findings for both were also inconclusive.With regard to adverse effects, there is very low-quality evidence that antidepressants increase dizziness and drowsiness (one RCT, 37 participants), and that alpha lipoic acid increased headache (two RCTs, 118 participants) and gastrointestinal complaints (3 RCTs, 138 participants). We found insufficient/contradictory evidence regarding adverse events for anticonvulsants or benzodiazepines. Adverse events were poorly reported or unreported for cholinergics, electromagnetic radiation, and psychological therapies. No adverse events occurred from physical barriers or topical therapy use. AUTHORS' CONCLUSIONS: Given BMS' potentially disabling nature, the need to identify effective modes of treatment for sufferers is vital. Due to the limited number of clinical trials at low risk of bias, there is insufficient evidence to support or refute the use of any interventions in managing BMS. Further clinical trials, with improved methodology and standardised outcome sets are required in order to establish which treatments are effective. Future studies are encouraged to assess the role of treatments used in other neuropathic pain conditions and psychological therapies in the treatment of BMS.

Orofacial pain: a guide for the headache physician.

Orofacial pain represents a significant burden in terms of morbidity and health service utilization. It includes very common disorders such as toothache and temporomandibular disorders, as well as rare orofacial pain syndromes. Many orofacial pain conditions have overlapping presentations, and diagnostic uncertainty is frequently encountered in clinical practice. This review provides a clinically orientated overview of common and uncommon orofacial pain presentations and diagnoses, with an emphasis on conditions that may be unfamiliar to the headache physician. A holistic approach to orofacial pain management is important, and the social, cultural, psychological and cognitive context of each patient needs to be considered in the process of diagnostic formulation, as well as in the development of a pain management plan according to the biopsychosocial model. Recognition of psychological comorbidities will assist in diagnosis and management planning.

Multi-dimensionality of chronic pain of the oral cavity and face.

Orofacial pain in its broadest definition can affect up to 7% of the population. Its diagnosis and initial management falls between dentists and doctors and in the secondary care sector among pain physicians, headache neurologists and oral physicians. Chronic facial pain is a long term condition and like all other chronic pain is associated with numerous co-morbidities and treatment outcomes are often related to the presenting co-morbidities such as depression, anxiety, catastrophising and presence of other chronic pain which must be addressed as part of management . The majority of orofacial pain is continuous so a history of episodic pain narrows down the differentials. There are specific oral conditions that rarely present extra orally such as atypical odontalgia and burning mouth syndrome whereas others will present in both areas. Musculoskeletal pain related to the muscles of mastication is very common and may also be associated with disc problems. Trigeminal neuralgia and the rarer glossopharyngeal neuralgia are specific diagnosis with defined care pathways. Other trigeminal neuropathic pain which can be associated with neuropathy is caused most frequently by trauma but secondary causes such as malignancy, infection and auto-immune causes need to be considered. Management is along the lines of other neuropathic pain using accepted pharmacotherapy with psychological support. If no other diagnostic criteria are fulfilled than a diagnosis of chronic or persistent idiopathic facial pain is made and often a combination of antidepressants and cognitive behaviour therapy is effective. Facial pain patients should be managed by a multidisciplinary team.

Management of chronic pain associated with temporomandibular disorders: a clinical practice guideline.

CLINICAL QUESTION: What is the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD)? CURRENT PRACTICE: TMD are the second most common musculoskeletal chronic pain disorder after low back pain, affecting 6-9% of adults globally. TMD are associated with pain affecting the jaw and associated structures and may present with headaches, earache, clicking, popping, or crackling sounds in the temporomandibular joint, and impaired mandibular function. Current clinical practice guidelines are largely consensus-based and provide inconsistent recommendations. RECOMMENDATIONS: For patients living with chronic pain (≥3 months) associated with TMD, and compared with placebo or sham procedures, the guideline panel issued: (1) strong recommendations in favour of cognitive behavioural therapy (CBT) with or without biofeedback or relaxation therapy, therapist-assisted mobilisation, manual trigger point therapy, supervised postural exercise, supervised jaw exercise and stretching with or without manual trigger point therapy, and usual care (such as home exercises, stretching, reassurance, and education); (2) conditional recommendations in favour of manipulation, supervised jaw exercise with mobilisation, CBT with non-steroidal anti-inflammatory drugs (NSAIDS), manipulation with postural exercise, and acupuncture; (3) conditional recommendations against reversible occlusal splints (alone or in combination with other interventions), arthrocentesis (alone or in combination with other interventions), cartilage supplement with or without hyaluronic acid injection, low level laser therapy (alone or in combination with other interventions), transcutaneous electrical nerve stimulation, gabapentin, botulinum toxin injection, hyaluronic acid injection, relaxation therapy, trigger point injection, acetaminophen (with or without muscle relaxants or NSAIDS), topical capsaicin, biofeedback, corticosteroid injection (with or without NSAIDS), benzodiazepines, and ß blockers; and (4) strong recommendations against irreversible oral splints, discectomy, and NSAIDS with opioids. HOW THIS GUIDELINE WAS CREATED: An international guideline development panel including patients, clinicians with content expertise, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel approached the formulation of recommendations from the perspective of patients, rather than a population or health system perspective. THE EVIDENCE: Recommendations are informed by a linked systematic review and network meta-analysis summarising the current body of evidence for benefits and harms of conservative, pharmacologic, and invasive interventions for chronic pain secondary to TMD. UNDERSTANDING THE RECOMMENDATION: These recommendations apply to patients living with chronic pain (≥3 months duration) associated with TMD as a group of conditions, and do not apply to the management of acute TMD pain. When considering management options, clinicians and patients should first consider strongly recommended interventions, then those conditionally recommended in favour, then conditionally against. In doing so, shared decision making is essential to ensure patients make choices that reflect their values and preference, availability of interventions, and what they may have already tried. Further research is warranted and may alter recommendations in the future.

Trigeminal neuralgia: the diagnosis and management of this excruciating and poorly understood facial pain.

Trigeminal neuralgia is defined as sudden, usually unilateral, severe, brief, stabbing recurrent episodes of pain within the distribution of one or more branches of the trigeminal nerve, which has a profound effect on quality of life. The diagnosis is made on history alone, and time needs to be taken to elicit the key features and differentiate from toothache or one of the trigeminal autonomic cephalalgias. Most trigeminal neuralgia is idiopathic, but a small percentage is due to secondary causes-for example, tumours or multiple sclerosis-which can be picked up on CT or MRI. Recently published international guidelines suggest that carbamazepine and oxcarbazepine are the first-line drugs. There is limited evidence for the use of lamotrigine and baclofen. If there is a decrease in efficacy or tolerability of medication, surgery needs to be considered. A neurosurgical opinion should be sought early. There are several ablative, destructive procedures that can be carried out either at the level of the Gasserian ganglion or in the posterior fossa. The only non-destructive procedure is microvascular decompression (MVD). The ablative procedures give a 50% chance of patients being pain free for 4 years, compared with 70% of patients at 10 years after MVD. Ablative procedures result in sensory loss, and MVD carries a 0.2-0.4% risk of mortality with a 2-4% chance of ipsilateral hearing loss. Surgical procedures result in markedly improved quality of life. Patient support groups provide information and support to those in pain and play a crucial role.

Dentists' and specialists' knowledge of chronic orofacial pain: results from a continuing professional development survey.

AIM: To explore the knowledge of chronic orofacial pain within general dental practitioners (GDPs) and dental specialists. METHODS: Following a recent national survey of GDPs and specialists on the diagnosis of facial pain, all those who responded were asked to answer four multiple-choice questions on chronic orofacial pain as part of a continuing professional development exercise. The questions were formulated using a review of the literature and consultation with a facial pain expert and were administered by post. RESULTS: Of the 380 subjects who completed the original survey, 212 (56%) returned completed multiple-choice questionnaires. Specialists correctly answered significantly more questions than GDPs (P<0.001). The majority of specialists-49/83 (59%)-obtained a score of three or more, compared to 39/129 (30%) GDPs. This was due to variation in answering one question. Significantly more specialists--50 (60%)--correctly selected trigeminal neuralgia (TN) as a condition that is not associated with COFP, whereas only 41 (32%) GDPs chose this answer. Both specialists and GDPs grossly underestimated the prevalence of COFP in secondary care clinics. CONCLUSIONS: The results suggest that specialists and GDPs may have sufficient knowledge to make an appropriate diagnosis of COFP, but they also highlight the knowledge gaps and perhaps the need for more extensive inclusion of COFP in the dental undergraduate curriculum.

Differential diagnosis for orofacial pain, including sinusitis, TMD, trigeminal neuralgia.

UNLABELLED: Correct diagnosis is the key to managing facial pain of non-dental origin. Acute and chronic facial pain must be differentiated and it is widely accepted that chronic pain refers to pain of 3 months or greater duration. Differentiating the many causes of facial pain can be difficult for busy practitioners, but a logical approach can be beneficial and lead to more rapid diagnoses with effective management. Confirming a diagnosis involves a process of history-taking, clinical examination, appropriate investigations and, at times, response to various therapies. CLINICAL RELEVANCE: Although primary care clinicians would not be expected to diagnose rare pain conditions, such as trigeminal autonomic cephalalgias, they should be able to assess the presenting pain complaint to such an extent that, if required, an appropriate referral to secondary or tertiary care can be expedited. The underlying causes of pain of non-dental origin can be complex and management of pain often requires a multidisciplinary approach.

Visual Imagery: A Tool to Explore the Impact of Burning Mouth Syndrome.

AIMS: To investigate how photographic images (Pain Cards) co-created by an artist and chronic pain patients could be used in groups of patients with burning mouth syndrome to facilitate characterization of their pain and its impact on quality of life. METHODS: Ten groups of patients with burning mouth syndrome attending a 2.5-hour information session in a facial pain unit were presented with 54 Pain Cards put in a random order on a table. They were asked to pick one card that described the quality of their pain and one that reflected the impact of the pain on their lives. The total number of patients was 119 (divided into groups of 8 to 14) over a 4-year period. RESULTS: A total of 114 patients chose a Pain Card; 24 cards (chosen a total of 73 times) were used to phenotype the pain and 39 cards (chosen a total of 127 times) were used to describe the impact of the pain. The most frequently used Pain Card (13 times) was a pair of lips closed with a clothes peg, whereas the other most frequently selected images were black and white. The choice of Pain Card and words used to explain the choice implied a neuropathic type of pain. Themes that were common included those of isolation, loss of confidence, low mood, and decrease in activities and socialization. CONCLUSION: The Pain Cards chosen and the main themes support those found in the literature on BMS. The Pain Cards may help pain sufferers gain more empathy and support due to improved understanding by their health care providers.

Diagnosis and management of non-dental orofacial pain.

UNLABELLED: Careful history-taking improves diagnosis of non-dental orofacial pain, a not uncommon group of conditions. Accurate diagnosis of conditions such as chronic idiopathic facial pain, temporomandibular disorders, burning mouth syndrome and trigeminal neuralgia is essential if inappropriate dental treatment is to be avoided. There are few investigations to help in the diagnostic process and many of these patients have other forms of chronic pain. All the conditions are best treated using a holistic approach. Drugs, such as tricyclic antidepressants and anticonvulsants, are often effective and surgery can be highly successfully in trigeminal neuralgia. Patient education is paramount. CLINICAL RELEVANCE: Although the majority of pain seen in general dental practice is dental in origin, chronic non-dental orofacial pain must be recognized as its management is entirely different.

Chronic/Persistent Idiopathic Facial Pain.

Persistent or chronic idiopathic facial pain, often called atypical facial pain, is often used as a diagnosis of exclusion. It is chronic pain in a nonanatomically distributed area of the face and mouth that can be episodic or continuous and described as a nagging dull pain that at times is severe. It is associated with other chronic pain conditions, psychological abnormalities, and significant life events. Investigations are all normal and early treatment can prevent chronicity. A multidisciplinary biopsychosocial approach with the use of antidepressants and cognitive behavior therapy provides the best chance of pain relief and improved quality of life.

Development and validation of the Manchester orofacial pain disability scale.

OBJECTIVE: To design and validate a self-administered instrument for assessing orofacial pain related disability in the general population. METHODS: The 32-item questionnaire was developed by open-ended interviews with patients attending dental hospital clinics and was subsequently tested on 171 community subjects with self-reported orofacial pain and 48 dental hospital patients. RESULTS: Construct validity of the instrument was demonstrated in three ways. First, levels of reported disability were greater in dental hospital patients than for community subjects reporting orofacial pain. Secondly, the instrument was able to detect differences in disability levels reported by community subjects who did and did not consult with a healthcare professional and those who had acute and chronic pain. Thirdly, amongst community subjects with pain, disability scores increased with higher pain intensity, pain duration and were greater amongst subjects who had sought a consultation. Results of factor analysis identified two constructs: physical and psychosocial disabilities, associated with orofacial pain. The Cronbach's alpha score was 0.78 and 0.92 for the physical and psychosocial constructs, respectively, and this along with item correlation values between 0.43 and 0.80 confirmed the internal consistency. CONCLUSION: We have therefore designed a valid instrument for assessing the impact of painful orofacial conditions in both community and clinic settings.

Trigeminal neuralgia: unilateral episodic facial pain.

Trigeminal neuralgia is a rare cause of episodic unilateral facial pain and often in the initial presentation dental causes need to be eliminated, as it frequently presents in the lower trigeminal divisions. The pain description is characteristic of electric shock-like pain that is light-touch provoked, paroxysmal, and occurring daily; the condition can go into remission for weeks or months, however. The first-line drug is either carbamazepine or oxcarbazepine and has to be started in low doses. Over 70% of patients will initially obtain immediate relief. If efficacy or tolerability becomes a problem, then referral to a secondary care specialist should be made. Magnetic resonance imaging (MRI) scans can determine if there is a symptomatic cause and whether surgery is indicated. Surgical options provide longest pain relief periods. Patients need to be given information about all treatment options so they can make a decision about treatment. This report is adapted from paineurope 2014; Issue 4, © Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be viewed via the Web site: www.paineurope.com , at which health professionals can find links to the original articles and request copies of the quarterly publication and access additional pain education and pain management resources.

Temporomandibular disorders, headaches and chronic pain.

Temporomandibular disorders (TMDs) are a major cause of non-dental orofacial pain with a suggested prevalence of 3% to 5% in the general population. TMDs present as unilateral or bilateral pain centered round the pre-auricular area and can be associated with clicking and limitation in jaw movements. It is important to ascertain if there are other comorbid factors such as headaches, widespread chronic pain and mood changes. A biopsychosocial approach is crucial with a careful explanation and self-care techniques encouraged.

Interventions for the treatment of burning mouth syndrome: a systematic review.

AIMS: To carry out a systematic review of previous studies to determine the effectiveness of any intervention vs placebo for relief of symptoms and improvement in quality of life of patients with burning mouth syndrome (BMS) and to assess the quality of the studies. METHODS: Electronic databases, conference proceedings, and bibliographies of identified publications were searched (up to September 2001) to identify relevant literature, irrespective of language of publication. Randomized controlled trials and controlled clinical trials of interventions used for the treatment of BMS in comparison to a placebo were included. The primary outcome was relief of burning/discomfort. The screening of studies, validity assessment, and data extraction were undertaken independently and in duplicate. Since statistical pooling of data was inappropriate, a qualitative assessment was undertaken. RESULTS: Seven trials, evaluating antidepressants, cognitive behavioral therapy, analgesics, hormone replacement therapy, and vitamin complexes, met the inclusion criteria. None of the trials was able to provide conclusive evidence of effectiveness. However, cognitive behavioral therapy may be beneficial in reducing the intensity of the symptoms. CONCLUSION: Given that the research evidence is, as yet, unable to provide clear, conclusive evidence of an effective intervention, clinicians need to provide support and understanding when dealing with BMS sufferers. Psychological interventions that help patients to cope with symptoms may be of some use, but promising and new approaches to treatment still need to be evaluated in good-quality randomized controlled trials.

Diagnosis and management of trigeminal neuropathic pains.

SUMMARY Trigeminal neuropathic pains have presented diagnostic and therapeutic challenges to providers. In addition, knowledge of pathophysiology, current classification systems, taxonomy and phenotyping of these conditions are incomplete. While trigeminal neuralgia is the most identifiable and studied, other conditions are being recognized and require distinct management approaches. Furthermore, other facial pain conditions such as atypical odontalgia and burning mouth syndrome are now considered to have neuropathic elements in their etiology. This article reviews current knowledge on the pathophysiology, diagnosis and management of neuropathic pain conditions involving the trigeminal nerve, to include: trigeminal neuralgia, trigeminal neuropathic pain (with traumatically induced neuralgia and atypical odontalgia) and burning mouth syndrome. Treatment modalities are reviewed based on current and best available evidence. Trigeminal neuralgia is managed with anticonvulsant drugs as the first line, with surgical options providing variable results. Trigeminal neuropathic pain is managed medically based on the guidelines for other neuropathic pain conditions. Burning mouth syndrome is also treated with a number of neuropathic medications, both topical and systemic. In all these conditions, patients need to be thoroughly educated about their condition, involved in its management, and be provided with supportive and adjunctive treatment resources.

Assessment and treatment of trigeminal neuralgia.

Patients with trigeminal neuralgia, a rare facial neuropathic pain, present to both medical and dental specialists. International guidelines on diagnosis and management of trigeminal neuralgia provide a useful framework for this article.

Medical management of trigeminal neuropathic pains.

IMPORTANCE OF THE FIELD: Although trigeminal neuralgia has traditionally been considered the prime neuralgic condition in the face region, other forms of neuropathic pain are now being more frequently recognized and require recognition and a different management approach. AREAS COVERED IN THIS REVIEW: This review principally covers medical management of trigeminal neuralgia; but also included is glossopharyngeal neuralgia, trigeminal neuropathic pain (atypical odontalgia) and burning mouth syndrome. Systematic reviews and guidelines will be discussed. WHAT THE READER WILL GAIN: An update will be provided of drug therapy for these relatively rare facial pains. TAKE HOME MESSAGE: Trigeminal neuralgia continues to be best managed using anticonvulsant drugs, the primary ones being carbamazepine and oxcarbazepine; baclofen may be helpful and, of the newly emerging drugs, pregabalin has potential. Glossopharyngeal neuralgia remains managed in the same way as trigeminal neuralgia. Trigeminal neuropathic pain is probably best managed according to guidelines used for the management of neuropathic pain, which include the use of tricyclic antidepressants, gabapentin, pregabalin, duloxetine, venalafaxine and topical lidocaine. Burning mouth syndrome is a neuropathic pain managed initially with topical clonazepam and then with other neuropathic drugs. Patients need to be involved in their management.

Burning mouth syndrome.

INTRODUCTION: Burning mouth syndrome mainly affects women, particularly after the menopause, when its prevalence may be 18% to 33%. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for burning mouth syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: anaesthetics (local), antidepressants, benzodiazepines (topical clonazepam), benzydamine hydrochloride, cognitive behavioural therapy (CBT), dietary supplements, and hormone replacement therapy (HRT) in postmenopausal women.