Does choice of anesthesia during stage 1 sacral neuromodulation testing influence outcomes?

INTRODUCTION: Staged sacral neuromodulation (SNM) testing has been shown to have a high rate of progression to permanent implantation for the management of voiding dysfunction. Stage 1 lead placement (SNM-I) can be performed under monitored anesthesia care (MAC) or general anesthesia (GA). MAC allows for interpretation of sensory and motor responses to optimize lead placement while GA only permits for motor assessment. However, patient discomfort and movement can make lead placement challenging during MAC. Herein we evaluate whether the anesthesia type impacts the progression rate to permanent implantation (SNM-II). MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent SNM-I in the operating room for wet overactive bladder between 2005 and 2023. Patients were divided into two groups based on the type of anesthesia used, MAC or GA. Clinical variables and progression to SNM-II were compared between cohorts. Progression to SNM-II was based on ≥50% symptomatic improvement during a 1-2 week trial period following SNM-I. RESULTS: Of 121 patients included in the study, 95 (79%) underwent MAC and 26 (21%) GA for SNM-I. No difference in the progression rate to SNM-II was noted between groups (MAC, 68/95 patients, 72%; GA, 19/26, 73%; p = 0.39). We also found no difference when comparing the GA group to the 26 most recent MAC patients (MAC, 20/26 patients, 77%; GA, 19/26, 73%; p = 0.48). CONCLUSION: Types of anesthesia for SNM-I did not affect rate of progression to SNM-II. The result lends support to the reliance on motor responses alone for lead placement during SNM-I.

Exploring Orthopedic Stem-Cell Approaches for Osteoarthritis Management: Current Trends and Future Horizons.

PURPOSE OF REVIEW: Osteoarthritis (OA) is a prevalent and debilitating condition characterized by joint degeneration and pain. Current treatment options aim to alleviate symptoms and slow disease progression but lack curative potential. Stem cell therapies have emerged as a promising alternative. This article explores the epidemiology, pathophysiology, clinical manifestations of hip and knee OA, and the evolving role of stem cell therapies in their treatment. RECENT FINDINGS: The global prevalence of OA, with knee OA being the most common form, has fueled the demand for stem cell therapies. Despite limited robust evidence supporting their efficacy, clinical trials investigating stem-cell treatments for OA have reported encouraging radiological and clinical improvements. Stem cell therapies offer potential disease-modifying benefits through immunomodulatory actions, growth factor secretion, and chondrogenic capabilities. Adipose-derived mesenchymal stem cells (ADMSCs) have shown promise in clinical trials for OA treatment, offering potential pain relief and functional improvement. ADMSCs possess advantages such as accessibility and a favorable safety profile, making them a viable option for OA management. Although other stem-cell types, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), have been used in OA treatment, ADMSCs have demonstrated superior outcomes. By providing a comprehensive overview of the evolving landscape of stem cell therapies for hip and knee OA, this article highlights the potential of stem-cell treatments to address the limitations of current therapies. However, further research is required to establish their long-term efficacy, identify optimal stem-cell types, and develop standardized protocols.

Stigmatization as a Barrier to Urologic Care: A Review.

Heavy societal stigma of certain conditions has created an environment where individuals may be hesitant to seek professional care. Urology is a specialized field that focuses on many of these conditions that society has deemed taboo to discuss. In this review, we address barriers that have prevented patients from seeking urologic care in order to better understand and elucidate important concerns within development of the physician-patient relationship. Recognizing these concerns can also assist in public health outreach approaches to motivate patients for seeking urologic care. The scope of this review was limited to three highly prevalent conditions affecting both men and women, including urinary incontinence, erectile dysfunction, and genitourinary syndrome of menopause.

Lower Urinary Tract Symptoms in Depression: A Review.

Lower Urinary Tract Symptoms (LUTS) are frequently present in the general population as patients age with approximately a third of individuals experiencing LUTS during their lifetime. LUTS can be further defined as having any of the following symptoms: urinary hesitancy, straining, nocturia, increased urination frequency, and dysuria. LUTS has the potential for patients to contribute their symptoms to what can normally occur as we age. This can lead to a decrease in patients seeking care and could negatively impact patients' health-related quality of life (HRQL). In conjunction with LUTS, we obtained from our analysis that LUTS and depression are closely related and worsening depressive symptoms may increase the severity of LUTS. We also discerned three categories of factors that can yield major depression namely adversity, internalizing, and externalizing factors. Within these categories, trauma, social support, genetic factors, and minimal education appeared to increase the risk of depression in patients. With the recent increase in mental health awareness and more access to mental health care amid the COVID-19 Pandemic, further screening, and collaboration between providers to treat both urological and psychiatric symptoms could improve patient outcomes. It is important for providers to have an increased understanding of the mental and physical impact both LUTS and depression can have on patients' wellbeing. This has the potential to help patients be more open about their symptoms with the aim of better addressing LUTS and depression to positively impact their HRQL.

Koro Syndrome: Epidemiology, Psychiatric and Physical Risk Factors, Clinical Presentation, Diagnosis, and Treatment Options.

Koro syndrome is a multi-tiered disease presenting as an overwhelming belief that one's sex organs are shrinking into their body. Moderate to severe anxiety attacks are associated with the condition, along with a fear of imminent death. Koro is often culturally related and is most seen as an epidemic form in East and Southeast Asia, although it can present anywhere worldwide in its sporadic form. The condition typically affects young males who believe in sex-related myths, and many individuals can co-present with anxiety, depression, or even psychosis. Although most presentations of Koro are self-limiting, the condition is harmful for one's self-esteem and quality of life, and some individuals may go through extreme, physically injurious measures to prevent genital retraction. Treatments include the use of psychotherapy that has a sex education component, especially if the patient believes in culturally rooted myths. In sporadic Koro, it is believed that if the primary psychiatric disorder is treated with anxiolytics, antidepressants, sedatives, or psychotics, the secondary Koro-like symptoms will also fade. Additional investigation on the prevalence, pathogenesis, factors that correlate with treatment efficacy are needed to fully understand Koro syndrome.

Vasectomy Regret Among Childless Men.

OBJECTIVE: To address historical concerns surrounding vasectomy in childless men, we sought to evaluate for the level of regret in this unique cohort. METHODS: The records of patients who underwent vasectomy via single surgeon between 2006 and 2021 were retrospectively reviewed and those who had not fathered children in any capacity at time of vasectomy were selected. We devised a 6-question survey inquiring about regret and thoughts on vasectomy reversal and assisted reproductive technology (ART). The questions are listed in Table 1. Patients were queried via a telephone call to rate their level of regret, both immediately after vasectomy and present day. The cohort was analyzed via age at time of vasectomy, time since vasectomy and marital status. RESULTS: There were 4812 overall patients who underwent vasectomy in this interval, with 205 (4.3%) who were childless. The response rate was 33.2% (68/205). Average age was 36.6 years with average time since vasectomy at time of phone call was 5.51 years. Regret rate was 4.4% immediately following vasectomy and 7.4% at time of telephone interview. A confirmatory, second consultation before vasectomy was present in 6.8% (14/205). The majority of patients 150/205 (73.1%) were married. When patients were stratified by marital status, there was no significant difference in any of the questions. The majority of patients were satisfied with their decision, with few contemplating or pursuing reversal or ART (Table 1). CONCLUSION: Regret in childless patients who undergo vasectomy is very rare, with the majority of patients feeling that their life was improved.

Prenatal diagnosis and delivery of megalencephaly-capillary malformation syndrome.

Hemimegalencephaly (HME) is a rare neurological diagnosis defined as hamartomatous overgrowth of one cerebral hemisphere. The hypothesised pathogenesis is due to an increased number or size of neural cells; however, the exact mechanism can vary widely, depending on the underlying aetiology. We report a case outlining the prenatal diagnostic process and obstetric considerations for delivering an infant with HME secondary to megalencephaly-capillary malformation syndrome. After diagnosis, our patient was induced and delivered at 37 weeks of gestation via operative vaginal delivery. To our knowledge, this is the first report describing the course from prenatal diagnosis through delivery of a fetus with HME.

Testosterone Replacement Therapy in the Treatment of Depression.

Background: Depression is a common disorder that affects millions globally and is linked to reduced quality of life and mortality. Its pathophysiology is complex and there are several forms of treatment proposed in the literature with differing side effect profiles. Many patients do not respond to treatment which warrants augmentation with other treatments and the investigation of novel treatments. One of these treatments includes testosterone therapy which evidence suggests might improve depressed mood in older patients with low levels of testosterone and helps restore physical impairments caused by age-related hormonal changes. Objective: The objective of this review is to synthesize information regarding clinical depression, its treatment options, and the efficacy and safety of testosterone treatment for the treatment of depression. Methods: This review utilized comprehensive secondary and tertiary data analysis across many academic databases and published work pertaining to the topic of interest. Results: Within some subpopulations such as men with dysthymic disorder, treatment resistant depression, or low testosterone levels, testosterone administration yielded positive results in the treatment of depression. Additionally, rodent models have shown that administering testosterone to gonadectomized male animals reduces symptoms of depression. Conversely, some studies have found no difference in depressive symptoms after treatment with testosterone when compared with placebo. It was also noted that over administration of testosterone is associated with multiple adverse effects and complications. Conclusion: The current evidence provides mixed conclusions on the effectiveness of testosterone therapy for treating depression. More research is needed in adult men to see if declining testosterone levels directly influence the development of depression.

Dhat Syndrome: Epidemiology, Risk Factors, Comorbidities, Diagnosis, Treatment, and Management.

Dhat syndrome is a culture-bound psychiatric syndrome most commonly found in the Indian subcontinent. It has been characterized as the experiential fear of losing semen through ejaculation, nocturnal emission, or other means. While Dhat syndrome is common in the Indian subcontinent, given the lack of representativeness, generalizability, and closer connection to Ayurvedic system, there have been limited studies or recognition of symptoms among healthcare providers around the world. In this review, we describe Dhat syndrome, its epidemiology, risk factors, comorbidities, diagnosis, treatment, and its management. For patients with Dhat syndrome, it becomes important to appreciate how generalized depression and anxiety may persist alongside the disorder and those symptoms can be common and non-specific. Related to its strong cultural connection with South Asia such as the belief on Dhat's role in health and vitality influence, it also becomes important to recognize that the syndrome can be found in other populations and the importance of cultural humility and nonconfrontational approach for patient care. In summary, this review provides an informative understanding of Dhat syndrome for non-Indian clinicians who may not be prepared for a patient encounter with vague somatic symptoms in the context of semen loss. Treatment for Dhat syndrome is the same as treatments for major depressive disorder.

Chaperones Utilization in Clinical Practice: Intimate and Sensitive Physical Examination Best Practice Strategies and Concepts in Modern Urological Medicine.

The intention of utilizing chaperones during sensitive physical exams is to show respect to the patient, while simultaneously providing protection to both the patient and the medical provider. Despite clinical practice recommendations to offer chaperones for sensitive urologic exams, there is no data regarding the consistency of chaperone utilization. Our aim was to summarize the patient and provider perspectives on the role of chaperones in urology as well as identify barriers to implement chaperone consistency. In the present investigation, we conducted a systematic review of prospective, case-control, and retrospective studies and followed the PRISMA 2020 guidelines for data reporting. Studies were identified from PubMed, MEDLINE, and PMC using the Medical Subject Headings (MeSH) terms "chaperones, patient", "chaperones, medical", and keywords "chaperones", and "urology". Studies were included if they addressed patient/provider perspectives on chaperone utilization in urology specifically and were excluded if they investigated perspectives on chaperone utilization in other specialties. Preliminary study identification yielded 702 studies, 9 of which were eligible for this review after applying the inclusion and exclusion criteria. Of these, 4 studies focused on the patient perspective and 5 focused on the provider perspective. The percentage of patients that did not have a chaperone present during their urologic exam ranged from 52.9-88.5%. A greater proportion of these patients were male. Patients (59%) prefer a family member compared to a staff member as a chaperone. Physicians (60%) prefer staff member chaperones compared to family members. One study reported that 25.6% of patients did not feel comfortable to ask for a chaperone if they were not offered one. Two studies reported the percentage of patients who believed chaperones should be offered to all urology patients, ranging from 73-88.4%. Three studies reported the use of chaperones in the clinic which ranged from 5-72.5%. Two studies reported chaperone utilization documentation, ranging between 16-21.3%. Two studies reported the likelihood of chaperone utilization depending on gender of the physician, showing that male physicians were more likely to utilize chaperones and were 3x more likely to offer chaperones to their patients compared to female physicians. Research suggests that there are differing perspectives between patients and physicians regarding the specific role and benefits chaperones offer during a sensitive urologic examination, as well as differences in preferences of who should perform the role of the chaperone. While more work needs to be done to bridge the divide between clinical practice and patient/physician preferences, the act of offering chaperones to urologic patients, regardless if they want to utilize a chaperone for their examination is respectful of patient privacy and decision making.

The Implications of Mental Health and Trauma in Interstitial Cystitis.

This review aims to assess the relationship between interstitial cystitis (IC) and significant traumatic events or PTSD. It was shown that there is a strong correlation between past trauma and the development of interstitial cystitis, as well as a much higher incidence of PTSD in patients diagnosed with IC. It was also established that for individuals with early traumatic experiences, the more likely the development of IC later in life, and with more severe symptoms and adverse effects on quality of life. We describe three distinct hypotheses for the possible physiologic mechanism for development of IC with relation to mental health and trauma, although definitive evidence in this area is still lacking, which poses interesting avenues for further research. This review also revealed an apparent lack of, and need for, trauma informed care and screening for PTSD in patients diagnosed with IC or other chronic pain syndromes.

Racial Disparities and Mental Health Effects Within Prostate Cancer.

Disparities in prostate cancer (PCa) exist at all stages: screening, diagnosis, treatment, outcomes, and mortality. Although there are a multitude of complex biological (e.g., genetics, age at diagnosis, PSA levels, Gleason score) and nonbiological (e.g., socioeconomic status, education level, health literacy) factors that contribute to PCa disparities, nonbiological factors may play a more significant role. One understudied aspect influencing PCa patients is mental health related to the quality of life. Overall, PCa patients report poorer mental health than non-PCa patients and have a higher incidence of depression and anxiety. Racial disparities in mental health, specifically in PCa patients, and how poor mental health impacts overall PCa outcomes require further study.

Gender Dysphoria and Its Non-Surgical and Surgical Treatments.

Gender dysphoria is defined by severe or persistent distress associated with an incongruence between one's gender identity and biological sex. It is estimated that 1.4 million Americans and 25 million people worldwide identify as transgender and that 0.6% of Americans experience gender dysphoria. The pathophysiology of gender dysphoria is multifactorial and incompletely understood. Genetics, androgen exposure, neuroanatomy, brain connectivity, history of trauma, parents with psychological disorders, and being raised by less than two parents are associated with gender dysphoria. Gender dysphoria most frequently presents in early teenage years but can present earlier or later. Anxiety and depression are the two most common comorbid diagnoses and may be the reason for presentation to medical care. Diagnosis is established through history and or validated questionnaires. Treatment includes psychosocial therapy, pharmacotherapy for underlying depression and/or anxiety, hormonal therapy, non-genital and/or genital feminization or masculinization operations. The frequency and severity of treatment related morbidity increases progressively as treatments go from conservative to more invasive. Gender dysphoria and its treatment is individualized and not completely understood.

Mental Health in Non-Oncologic Urology Patients.

This article is a literature review of mental health concerns in non-oncologic urology patients. Pathologies represented in this review include Peyronie's Disease (PD), erectile dysfunction (ED), urinary incontinence and urinary tract infections (UTI), infertility, benign prostatic hyperplasia (BPH), kidney stones, and urinary retention. While there has been great interventional focus as of late for urogenitary malignancies (i.e. prostate cancer awareness with the Movember campaign), literature studies and intervention focused on non-oncologic urology patients has been limited. As such, we conducted a review on urology patients with non-oncologic pathologies as an effort to increase clinician awareness of mental health concerns among such patients, increase the comfort level for clinician communication on socially sensitive topics surrounding pathologies, and review ongoing interventions conducted within these pathologies. We outlined different ongoing Mental Health Illness (MHI) needs and treatments for various pathologies. Patients with non-cancerous urologic pathologies had lower quality of life and higher incidence of MHI than the general population. As such, in line with the American Urological Association recommendations, psychological and social support from peers, therapists, and healthcare providers further prove to be crucial for some subpopulations. The review also yielded pathology specific interventions such as group therapy for ED patients. Given the higher incidence of MHI in the patient population after the Covid-19 pandemic, MHI awareness in the sphere of non-oncologic urology treatment continues to be crucial when creating a collaborative treatment platform for patients.

Vasectomy Regret or Lack Thereof.

Background: Vasectomy is a procedure that results in permanent yet reversible sterility and remains a great contraceptive option for many. Previous research studies have highlighted frequency of vasectomy utilization, defining characteristics of individuals who opt for this method, various surgical techniques, and the risks and benefits associated with the procedure. What remains to be defined is why or why not individuals may experience post-vasectomy regret and whether the previous characteristics correlate. Objective: The objective of this review is to synthesize information regarding reasons individuals may regret their vasectomy and seek reversal, what options exist for accomplishing the reversal, and patients' fertility prognosis post-vasovasostomy. Methods: This review utilized a combination of secondary and tertiary data analysis across a wide scope of academic databases pertaining to the topic of interest. Results: Typically, most males who have sought a vasectomy are satisfied with their decision, however, approximately 6% of this population seeks reversal. Key factors influencing vasectomy regret include age at the time of vasectomy, parental status, pre- and post-operative relationship status, unresolved physical and psychosexual problems, and development of chronic scrotal pain following the procedure. Few options exist for vasectomy reversal including microsurgical reconstructive vasectomy reversal (VR) and sperm extraction for in vitro fertilization. There is no guarantee that fertility will be restored in any case but a major predictive factor for success is the time interval prior to reversal. Conclusion: Vasectomy is intended to be a permanent form of contraception; however, a minor chance remains that individuals may experience post-operative regret due to various factors. This warrants proper comprehensive counseling by the patient's provider regarding benefits and risks, procedural outcomes, opportunities for reversal, and fertility prognosis.

Ketamine-Induced Cystitis: A Comprehensive Review of the Urologic Effects of This Psychoactive Drug.

Ketamine is a common medical anesthetic and analgesic but is becoming more widely used as a recreational drug. Significant side effects on the urinary tract are associated with frequent recreational ketamine use most notably ketamine-induced cystitis (KIC). Regular ketamine consumption has been shown to increase the risk of cystitis symptoms by 3- to 4-fold, and cessation of ketamine use is usually associated with improvement of symptoms. Common KIC-related problems are urinary pain and discomfort, bladder epithelial barrier damage, reduced bladder storage and increased pressure, ureter stenosis, and kidney failure, all of which significantly impact patients' quality of life. Furthermore, it becomes a vicious cycle when KIC patients attempt to manage their urinary pain with increased ketamine use. The precise pathophysiology of KIC is still unknown but several theories exist, most of which highlight the inflammatory signaling pathways leading to bladder epithelium damage due to presence of ketamine in the urine. Empirical treatment options for KIC are available and consist of ketamine cessation, noninvasive therapies, and surgery, and should be decided upon based on the time course and severity of the disease. Of note, cessation of use is strongly recommended for all KIC patients, and should be supplemented with motivational interviews and psychological and social support. It is crucial for clinicians to be familiar with KIC diagnosis and treatment, and to be prepared to have informed discussions with ketamine-using patients about the potential health consequences of ketamine.

Opioids in Urology: How Well Are We Preventing Opioid Dependence and How Can We Do Better?

Urologic procedures (both open and minimally invasive) can cause pain due to the surgery itself, devices placed, and post-operative issues. Thus, pain management is important for every post-procedure recovery period. Opioid use post-surgery is common and often over-prescribed contributing to persistent use by patients. In this article, we review the extent of opioid use in pediatric urologic procedures, vasectomy, endourologic procedures, penile implantation, urogynecologic procedures, prostatectomy, nephrectomy, cystectomy, and scrotal/testicular cancer surgery. Generally, we have found that institutions do not have a standardized protocol with a set regimen to prescribe opioids, resulting in more opioids being prescribed than needed and patients not properly disposing of their unused prescriptions. However, many institutions recognize their opioid overuse and are implementing new multimodal opioid-sparing analgesics methods such as non-opioid peri-operative medications, minimally invasive robotic surgery, and nerve blocks or local anesthetics with varying degrees of success. By shedding light on these opioid-free methods and prescription protocols, along with improved patient education and counselling, we hope to bring awareness to institutions and decrease unnecessary opioid use.

A Comprehensive Review of Cubital Tunnel Syndrome.

Cubital Tunnel Syndrome (CuTS) is the compression of the ulnar nerve as it courses through the cubital tunnel near the elbow at the location colloquially referred to as the "funny bone". CuTS is the most commonly diagnosed mononeuropathy after carpal tunnel syndrome. Cubital tunnel syndrome can manifest as numbness, tingling, or pain in the ring/small fingers and dorsoulnar hand. Repetitive pressure, stretching, flexion, or trauma of the elbow joint are known causes of CuTS. Chronic ulnar nerve compression and CuTS, when left untreated, can lead to atrophy of the first dorsal interosseus muscle and affect one's quality of life to the point that they are no longer able to participate in daily activities involving fine motor function. It is estimated that up to 5.9% of the general population have had symptoms of CuTS. CuTS is underdiagnosed due to lack of seeking of treatment for symptoms. Compression or damage to the ulnar nerve is the main cause of symptoms experienced by an individual with CuTS. Repetitive elbow pressure or a history or elbow joint trauma or injury are additional known causes that can lead to CuTS. Common presentations of CuTS include paresthesia, clumsiness of the hand, hand atrophy and weakness. The earliest sign of CuTS is most commonly numbness and tingling of the ring and 5th finger. Older patients tend to present with motor symptoms of chronic onset; younger patients tend to have more acute symptoms. Pain and point tenderness at the medial elbow may also be seen. CuTS lacks universally agreed upon diagnostic and treatment algorithms. CuTS can be diagnosed by physical exam using Tinel's sign, flexion-compression tests, palpating the ulnar nerve for thickening presence of local tenderness along the nerve. Ultrasound and nerve conduction studies may be used in combination with physical exam for diagnosis. Conservative treatment for CuTS is almost always pursued before surgical treatment and includes elbow splints, braces, and night-gliding exercises. Surgical treatment may be pursued in severe CuTS refractory to conservative treatment. Surgical options include open and endoscopic in-situ decompression, medial epicondylectomy, and anterior transposition of the ulnar nerve. CuTS is a prevalent disease that, if left untreated, can significantly alter an individual's quality of life. Therefore, an accurate diagnosis and appropriate treatment is paramount in reducing further damage and preventing worsening or future symptoms.

Second Case of Tumors Associated With Heterozygous NTHL1 Variant.

Homozygous mutations to NTHL1 are known to increase cancer risk, particularly in the colon and breast. NTHL1 tumor syndrome (NTS) is an autosomal recessive genetic condition. Little is known about the cancer risk in patients who have heterozygous NTHL1 mutations. We previously published a case of benign tumors associated with a heterozygous NTHL1 mutation. In this second case, we present a patient with a heterozygous NTHL1 mutation who developed a gastrointestinal stromal tumor, pilocytic astrocytoma, tall cell papillary thyroid cancer, invasive ductal papilloma, spinal nerve sheath tumors, and spinal hemangiomas. Here, we show that heterozygous NTHL1 mutations may increase cancer risk and may even manifest similarly to NTS.

Male Sexual Dysfunction.

Male sexual dysfunction is a series of conditions, most notably including erectile dysfunction (ED), Peyronie's disease (PD), and premature ejaculation (PE), defined by impaired sexual functioning. The prevalence of male sexual dysfunction increases with age and is relatively high with greater than 50% of men aged 40 to 70 describing some degree of erectile dysfunction. Risk factors for male sexual dysfunction include age, diabetes mellitus (DM), cancer, stroke, hypertension, penile trauma, depression, anxiety, and disturbance in central serotonin neurotransmission and 5-HT postsynaptic receptor functioning. Sexual questionnaires including the International Index of Erectile Dysfunction, Sexual Health Inventory for Men, and the Premature Ejaculation Diagnostic Tool are useful in screening for these disorders. Focused history and physical can establish diagnoses. For a condition to be diagnosed as male sexual dysfunction, the patient or their partner must view their sexual functioning as impaired. Treatment of male sexual dysfunction is etiology dependent. For ED, first-line therapy is a phosphodiesterase-5 inhibitor or mental health care for psychogenic ED. More complicated cases may be treated with injections, surgery, or shockwave therapy. PD is either treated with medications for pain management, collagenase clostridium histolyticum injection, corpoplasty, plication, or shockwave therapy. PE may be treated behaviorally or with SSRIs as first line medication.