Repetitive transcranial magnetic stimulation for generalized anxiety and panic disorders: A systematic review and meta-analysis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved, noninvasive modality for treating major depressive disorder and obsessive-compulsive disorder. Earlier studies evaluating therapeutic effects of rTMS on symptom scores of patients with generalized anxiety disorder (GAD) and panic disorder (PD) have yielded inconsistent findings. METHODS: We performed a systematic review and meta-analysis of interventional studies assessing the effect of rTMS on symptom scores in patients with GAD or PD with or without psychiatric comorbidities using studies published up to April 2021. We used DerSimonian-Laird random effects models to obtain pooled standardized mean difference (SMD) and 95% CI. RESULTS: A total of 13 studies consisting of 677 participants (404 treated with rTMS and 273 without rTMS) were included in this meta-analysis. In GAD patients with or without any comorbidities, rTMS therapy demonstrated significant improvements in anxiety (SMD = 1.45; P < .001) and depression (SMD = 1.65; P < .001) scores regardless of rTMS parameters. Overall anxiety (SMD = 0.24; P = .48) and panic severity (SMD = 1.19; P = .054) scores did not significantly improve after rTMS therapy in patients with PD. CONCLUSIONS: rTMS is safe and improves anxiety and depression scores only in GAD patients, regardless of underlying comorbidities or rTMS parameters.

Panic and pandemic: Narrative review of the literature on the links and risks of panic disorder as a consequence of the SARS-CoV-2 pandemic.

Although the "panic" word has been abundantly linked to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic in the press, in the scientific literature very few studies have considered whether the current epidemic could predispose to the onset or the aggravation of panic attacks or panic disorder. Indeed, most studies thus far have focused on the risk of increase and aggravation of other psychiatric disorders as a consequence of the SARS-CoV-2 epidemic, such as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Yet, risk of onset or aggravation of panic disorder, especially the subtype with prominent respiratory symptoms, which is characterized by a fear response conditioning to interoceptive sensations (e.g., respiratory), and hypervigilance to these interoceptive signals, could be expected in the current situation. Indeed, respiratory symptoms, such as coughs and dyspnea, are among the most commonly associated with the SARS-CoV-2 (59-82% and 31-55%, respectively), and respiratory symptoms are associated with a poor illness prognosis. Hence, given that some etiological and maintenance factors associated with panic disorder - i.e., fear conditioning to abnormal breathing patterns attributable or not to the COVID-19 (coronavirus disease 2019), as well as hypervigilance towards breathing abnormalities - are supposedly more prevalent, one could expect an increased risk of panic disorder onset or aggravation following the COVID-19 pandemic in people who were affected by the virus, but also those who were not. In people with the comorbidity (i.e., panic disorder or panic attacks and the COVID-19), it is particularly important to be aware of the risk of hypokalemia in specific at-risk situations or prescriptions. For instance, in the case of salbutamol prescription, which might be overly used in patients with anxiety disorders and COVID-19, or in patients presenting with diarrhea and vomiting. Hypokalemia is associated with an increased risk of torsade de pointe; thus, caution is required when prescribing specific psychotropic drugs, such as the antidepressants citalopram and escitalopram, which are first-line treatments for panic disorder, but also hydroxyzine, aiming at anxiety relief. The results reviewed here highlight the importance of considering and further investigating the impact of the current pandemic on the diagnosis and treatment of panic disorder (alone or comorbid with the COVID-19).

[Rivastigmine as treatment for flashbacks and REM sleep problems in an older patient]. / Rivastigmine tegen herbelevingen en remslaapstoornissen bij een oudere patiënte.

A 61-year-old woman with suspected schizophrenia has been attending an outpatient geriatrics service for some time, initially with memory complaints and panic attacks. During treatment, the diagnosis schizophrenia was rejected and psychopharmaceuticals were largely phased out, which improved cognitive functions. Eventually, flashbacks of incest experienced in childhood remained together with REM sleep pathology. The flashbacks, nightmares and the REM sleep pathology were responsive to rivastigmine. Rivastigmine use for the treatment of REM sleep pathology is known in the literature, but it has never been described previously that rivastigmine also impacts on flashbacks and nightmares..

The Adaptive Effect of Illness-Specific Panic-Fear on Asthma Outcomes in Mexican and Puerto Rican Children.

OBJECTIVE: To examine baseline measures of illness-specific panic-fear (ie, the level of anxiety experienced specifically during asthma exacerbations) as a protective factor in pediatric asthma outcomes over a 1-year period. STUDY DESIGN: The sample comprised 267 children (Mexican, n = 188; Puerto Rican, n = 79; age 5-12 years) from a longitudinal observational study conducted in Phoenix, AZ and Bronx, NY. Assessments were done at baseline and 3, 6, 9, and 12 months. The Childhood Asthma Symptom Checklist was administered at baseline to children and caregivers to assess children's illness-specific panic-fear. Asthma outcome variables quantified longitudinally included pulmonary function, the Asthma Control Test, acute healthcare utilization, and medication adherence, measured by devices attached to inhaled corticosteroids. RESULTS: Child report of illness-specific panic-fear at baseline predicted higher forced expiratory volume in 1 second (FEV1) % across 1-year follow-up in Mexican children (ß = 0.17, P = .02), better asthma control in Puerto Rican children (ß = 0.45, P = .007), and less acute healthcare utilization for asthma in both groups (Mexicans: ß = -0.39, P = .03; Puerto Ricans: ß = -0.47, P = .02). Caregiver report of child panic-fear predicted higher FEV1% in Mexican (ß = 0.30; P = .02) and Puerto Rican (ß = 0.19; P = .05) children. Panic-fear was not related to medication adherence. CONCLUSIONS: Illness-specific panic-fear had beneficial effects on asthma outcomes in both groups of Latino children. The heightened vigilance associated with illness-specific panic-fear may lead children to be more aware of their asthma symptoms and lead to better strategies for asthma management.

Anxiety Disorders in Adults With Childhood Traumatic Brain Injury: Evidence of Difficulties More Than 10 Years Postinjury.

OBJECTIVE: To explore long-term psychiatric outcomes in individuals with a history of childhood traumatic brain injury (TBI) or orthopedic injury (OI). SETTING: Hospital emergency department, medical admission records and outpatient settings. PARTICIPANTS: There were 95 males (M = 22.78 years, SD = 3.44 years) and 74 females (M = 22.27 years, SD = 3.09 years), 65 with mild TBI (M = 23.25 years, SD = 3.58 years), 61 with moderate-severe TBI (M = 22.34 years, SD = 2.79 years), and 43 with OI (M = 21.81 years, SD = 3.36 years). DESIGN: Longitudinal, between-subjects, cross-sectional design using retrospective and current data. MAIN MEASURES: Semistructured interview to obtain psychiatric diagnoses and background information, and medical records for identification of TBI. RESULTS: Group with moderate-severe TBI presented with significantly higher rates of any anxiety disorder (χ2 = 6.81, P = .03) and comorbid anxiety disorder (χ2 = 6.12, P < .05). Group with overall TBI presented with significantly higher rates of any anxiety disorder (χ1 = 5.36, P = .02), panic attacks (χ1 = 4.43, P = .04), specific phobias (χ1 = 4.17, P = .04), and depression (χ1 = 3.98, P < .05). Prediction analysis revealed a statistically significant model (χ7 = 41.84, P < .001) explaining 23% to 37% of the variance in having any anxiety disorder, with significant predictors being group (TBI) and gender (female). CONCLUSIONS: Children who have sustained a TBI may be vulnerable to persistent anxiety, panic attacks, specific phobias, and depression, even 13 years after the injury event.

Migraine-Like Visual Auras Among Traumatized Cambodians with PTSD: Fear of Ghost Attack and Other Disasters.

This article profiles visual auras among traumatized Cambodian refugees attending a psychiatric clinic. Thirty-six percent (54/150) had experienced an aura in the previous 4 weeks, almost always phosphenes (48% [26/54]) or a scintillating scotoma (74% [40/54]). Aura and PTSD were highly associated: patients with visual aura in the last month had greater PTSD severity, 3.6 (SD = 1.8) versus 1.9 (SD = 1.6), t = 10.2 (df = 85), p < 0.001, and patients with PTSD had a higher rate of visual aura in the last month, 69% (22/32) versus 13% (7/55), odds ratio 15.1 (5.1-44.9), p < 0.001. Patients often had a visual aura triggered by rising up to the upright from a lying or sitting position, i.e., orthostasis, with the most common sequence being an aura triggered upon orthostasis during a migraine, experienced by 60% of those with aura. The visual aura was often catastrophically interpreted: as the dangerous assault of a supernatural being, most commonly the ghost of someone who died in the Pol Pot period. Aura often triggered flashback. Illustrative cases are provided. The article suggests the existence of local biocultural ontologies of trauma as evinced by the centrality of visual auras among Cambodian refugees.

Impact of childhood trauma on course of panic disorder: contribution of clinical and personality characteristics.

OBJECTIVE: To investigate the impact of childhood trauma on the clinical course of panic disorder and possible contributing factors. METHOD: Longitudinal data of 539 participants with a current panic disorder were collected from the Netherlands Study of Depression and Anxiety (NESDA). Childhood trauma was assessed with a structured interview and clinical course after 2 years with a DSM-IV-based diagnostic interview and the Life Chart Interview. RESULTS: At baseline, 54.5% reported childhood trauma, but this was not predictive of persistence of panic disorder. Emotional neglect and psychological abuse were associated with higher occurrence of anxiety disorders other than panic disorder (social phobia) and with higher chronicity of general anxiety symptoms (anxiety attacks or episodes and avoidance). Baseline clinical features (duration and severity of anxiety and depressive symptoms) and personality traits (neuroticism and extraversion) accounted for roughly 30-60% of the total effect of childhood trauma on chronicity of anxiety symptoms and on occurrence of other anxiety disorders. CONCLUSION: After two years, childhood trauma is associated with chronicity of anxiety symptoms and occurrence of social phobia, rather than persistence of panic disorder. These relationships are partially accounted for by duration and severity of anxiety and depressive symptoms, and neuroticism and extraversion.

Panic Disorder in Patients Presenting to the Emergency Department With Chest Pain: Prevalence and Presenting Symptoms.

BACKGROUND: Patients with panic disorder experience symptoms such as palpitations, chest pain, dizziness, and breathlessness. Consequently, they may attend the Emergency Department (ED) to be assessed for possible emergency medical conditions. Recognition of panic disorder within the ED is low. We sought to establish the prevalence of panic disorder in patients presenting for ED investigation of potential acute coronary syndrome. We also sought to characterise the cohort of patients with panic disorder in terms of presenting symptoms, risk factors, medical history and major adverse cardiac events (MACE). METHODS: This was an observational study of 338 adult patients presenting to the Emergency Department of a tertiary hospital in Australia. Research nurses collected clinical data using a customised case report form. The outcome was panic disorder, assessed using the Mini International Neuropsychiatric Interview. RESULTS: The average age of participants was 50.2 years and 37.9% were female. Thirty-day MACE occurred in 7.7% of the cohort. The clinical diagnosis of panic disorder was made in 5.6% (95% CI: 3.4-8.6%) of patients. Compared to patients without panic disorder, patients with panic disorder were slightly more likely to report that their pain felt heavy (48.9% and 73.7% respectively, p=0.04). All other reported symptoms were similar in the two groups. CONCLUSIONS: The prevalence of panic disorder was low in patients presenting to an Australian ED with chest pain. Clinical signs or symptoms that are routinely collected as part of the chest pain workup cannot be used to distinguish patients with and without panic disorder.

[The power plants of the cell: Treatment of psychiatric symptoms in patients with mitochondriopathy]. / Die Kraftwerke der Zellen- über die Behandlung von psychiatrischen Symptomen bei Patienten mit Mitochondriopathien.

Introduction Mitochondriopathies are pathologies of cell organelles, which are essential for the formation of adenosine triphosphate (ATP), which is responsible for cellular energy stock. When mitochondrial mutations occur, symptoms arise frequently in those organs that rely on a continuous energy supply, such as the nervous system. Although psychiatric illness is increasingly prevalent in patients with mitochondrial disease, less attention has been paid to its psychiatric presentations. Case Report We describe a case of a 21-year-old woman who presented in our outpatient department with panic attacks and depression. The patient experienced major side effects after low-dose sertraline therapy. Conclusion Mitochondriopathies belong to the class of rare illnesses in psychiatry; nevertheless, they require adaptations of psychopharmacological therapy. Psychotropic drugs are potential respiratory chain inhibitors and could lead to distinct side effects.

The stability and change of etiological influences on depression, anxiety symptoms and their co-occurrence across adolescence and young adulthood.

BACKGROUND: Depression and anxiety persist within and across diagnostic boundaries. The manner in which common v. disorder-specific genetic and environmental influences operate across development to maintain internalizing disorders and their co-morbidity is unclear. This paper investigates the stability and change of etiological influences on depression, panic, generalized, separation and social anxiety symptoms, and their co-occurrence, across adolescence and young adulthood. METHOD: A total of 2619 twins/siblings prospectively reported symptoms of depression and anxiety at mean ages 15, 17 and 20 years. RESULTS: Each symptom scale showed a similar pattern of moderate continuity across development, largely underpinned by genetic stability. New genetic influences contributing to change in the developmental course of the symptoms emerged at each time point. All symptom scales correlated moderately with one another over time. Genetic influences, both stable and time-specific, overlapped considerably between the scales. Non-shared environmental influences were largely time- and symptom-specific, but some contributed moderately to the stability of depression and anxiety symptom scales. These stable, longitudinal environmental influences were highly correlated between the symptoms. CONCLUSIONS: The results highlight both stable and dynamic etiology of depression and anxiety symptom scales. They provide preliminary evidence that stable as well as newly emerging genes contribute to the co-morbidity between depression and anxiety across adolescence and young adulthood. Conversely, environmental influences are largely time-specific and contribute to change in symptoms over time. The results inform molecular genetics research and transdiagnostic treatment and prevention approaches.

Contribution of the Mission in Afghanistan to the Burden of Past-Year Mental Disorders in Canadian Armed Forces Personnel, 2013.

OBJECTIVE: The purpose of this study was to estimate the contribution of the mission in Afghanistan to the burden of mental health problems in the Canadian Armed Forces (CAF). METHODS: Data were obtained from the 2013 Canadian Forces Mental Health Survey, which assessed mental disorders using the World Health Organization's Composite International Diagnostic Interview. The sample consisted of 6696 Regular Force (RegF) personnel, 3384 of whom had deployed in support of the mission. We estimated the association of past-year mental health problems with Afghanistan deployment status, adjusting for covariates using logistic regression; population attributable fractions (PAFs) were also calculated. RESULTS: Indication of a past-year mental disorder was identified in 18.4% (95% confidence interval [CI], 17.0% to 19.7%) of Afghanistan deployers compared with 14.6% (95% CI, 13.3% to 15.8%) in others. Afghanistan-related deployments contributed to the burden of a past-year disorder (PAF = 8.7%; 95% CI, 3.0% to 14.2%), with the highest PAFs being seen for panic disorder (34.7%) and posttraumatic stress disorder (32.1%). The PAFs for individual alcohol use disorders and suicide ideation were not different from zero. Child abuse, however, had a much greater PAF for any past-year disorder (28.7%; 95% CI, 23.4% to 33.7%) than did the Afghanistan mission. CONCLUSIONS: The mission in Afghanistan contributed significantly to the burden of mental disorders in the CAF RegF in 2013. However, the much stronger contribution of child abuse highlights the need for strong military mental health systems, even in peacetime, and the need to target the full range of determinants of mental health in prevention and control efforts.

The role of perceived control over anxiety in prospective symptom reports across the menstrual cycle.

The present investigation tested the role of psychological vulnerabilities to anxiety in reported menstrual symptom severity. Specifically, the current study tested the incremental validity of perceived control over anxiety-related events in predicting menstrual symptom severity, controlling for the effect of anxiety sensitivity, a documented contributor to menstrual distress. It was expected that women with lower perceived control over anxiety-related events would report greater menstrual symptom severity, particularly in the premenstrual phase. A sample of 49 normally menstruating women, aged 18-47 years, each prospectively tracked their menstrual symptoms for one cycle and completed the Anxiety Control Questionnaire (Rapee, Craske, Brown, & Barlow Behav Ther 27:279-293. doi: 10.1016/S0005-7894(96)80018-9 , 1996) in their follicular and premenstrual phases. A mixed model analysis revealed perceived control over anxiety-related events was a more prominent predictor of menstrual symptom severity than anxiety sensitivity, regardless of the current cycle phase. This finding provides preliminary evidence that perceived control over anxiety-related events is associated with the perceived intensity of menstrual symptoms. This finding highlights the role of psychological vulnerabilities in menstrual distress. Future research should examine whether psychological interventions that target cognitive vulnerabilities to anxiety may help reduce severe menstrual distress.

Diagnosis and management of generalized anxiety disorder and panic disorder in adults.

Generalized anxiety disorder (GAD) and panic disorder (PD) are among the most common mental disorders in the United States, and they can negatively impact a patient's quality of life and disrupt important activities of daily living. Evidence suggests that the rates of missed diagnoses and misdiagnosis of GAD and PD are high, with symptoms often ascribed to physical causes. Diagnosing GAD and PD requires a broad differential and caution to identify confounding variables and comorbid conditions. Screening and monitoring tools can be used to help make the diagnosis and monitor response to therapy. The GAD-7 and the Severity Measure for Panic Disorder are free diagnostic tools. Successful outcomes may require a combination of treatment modalities tailored to the individual patient. Treatment often includes medications such as selective serotonin reuptake inhibitors and/or psychotherapy, both of which are highly effective. Among psychotherapeutic treatments, cognitive behavior therapy has been studied widely and has an extensive evidence base. Benzodiazepines are effective in reducing anxiety symptoms, but their use is limited by risk of abuse and adverse effect profiles. Physical activity can reduce symptoms of GAD and PD. A number of complementary and alternative treatments are often used; however, evidence is limited for most. Several common botanicals and supplements can potentiate serotonin syndrome when used in combination with antidepressants. Medication should be continued for 12 months before tapering to prevent relapse.

Efficacy, tolerability, and safety of hypnosis in adult irritable bowel syndrome: systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy, tolerability, and safety of hypnosis in adult irritable bowel syndrome by a meta-analysis of randomized controlled trials. METHODS: Studies were identified by a literature search of the databases Allied and Complementary Medicine Database, Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, PubMed, PsycINFO, and Scopus (from inception to June 30, 2013). Primary outcomes were adequate symptom relief, global gastrointestinal score, and safety. Summary relative risks (RRs) with number needed to treat (NNT) and standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated using random-effects models. RESULTS: Eight randomized controlled trials with a total of 464 patients and a median of 8.5 (7-12) hypnosis sessions over a median of 12 (5-12) weeks were included into the analysis. At the end of therapy, hypnosis was superior to control conditions in producing adequate symptom relief (RR, 1.69 [95% CI = 1.14-2.51]; NNT, 5 [3-10]) and in reducing global gastrointestinal score (SMD, 0.32 [95% CI = -0.56 to -0.08]). At long-term follow-up, hypnosis was superior to controls in adequate symptom relief (RR, 2.17 [95% CI = 1.22-3.87]; NNT, 3 [2-10]), but not in reducing global gastrointestinal score (SMD, -0.57 [-1.40 to 0.26]). One (0.4%) of 238 patients in the hypnosis group dropped out due to an adverse event (panic attack). CONCLUSION: This meta-analysis demonstrated that hypnosis was safe and provided long-term adequate symptom relief in 54% of patients with irritable bowel syndrome refractory to conventional therapy.

Association between latent toxoplasmosis and major depression, generalised anxiety disorder and panic disorder in human adults.

Latent infection with the apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with schizophrenia, bipolar disorder and self-harm behaviour. However, the potential relationship between T. gondii immunoglobulin G antibody (IgG) seropositivity and generalised-anxiety disorder (GAD) and panic disorder (PD) has not been investigated. The associations between serum reactivity to T. gondii and major depressive disorder (MDD), GAD and PD were evaluated in a total sample of 1 846 adult participants between the ages of 20 and 39 years from the United States Center for Disease Control's National Health and Nutrition Examination Survey (NHANES). Approximately 16% of the overall sample was seropositive for T. gondii and 7% of the sample met criteria for MDD, 2% for GAD and 2% for PD. There were no significant associations between T. gondii IgG seroprevalence and MDD (OR = 0.484, 95% CI = 0.186-1.258), GAD (OR = 0.737, 95% CI = 0.218-2.490) or PD (OR = 0.683, 95% CI = 0.206-2.270) controlling for sex, ethnicity, poverty-to-income ratio and educational attainment. However, limited evidence suggested a possible association between absolute antibody titres for T. gondii and GAD and PD but not MDD. Toxoplasma gondii seroprevalence was not associated with MDD, GAD or PD within the context of the limitations of this study, although there may be an association of T. gondii serointensity with and GAD and PD, which requires further study.

[Panic disorder: clinical features and treatment approaches].

The paper reviews scientific publications on studies of the epidemiology, etiology, pathogenesis, and main clinical manifestations of panic disorders and approaches to their treatment.

Low serum concentrations of vitamin B6 and iron are related to panic attack and hyperventilation attack.

Patients undergoing a panic attack (PA) or a hyperventilation attack (HVA) are sometimes admitted to emergency departments (EDs). Reduced serotonin level is known as one of the causes of PA and HVA. Serotonin is synthesized from tryptophan. For the synthesis of serotonin, vitamin B6 (Vit B6) and iron play important roles as cofactors. To clarify the pathophysiology of PA and HVA, we investigated the serum levels of vitamins B2, B6, and B12 and iron in patients with PA or HVA attending an ED. We measured each parameter in 21 PA or HVA patients and compared the values with those from 20 volunteers. We found that both Vit B6 and iron levels were significantly lower in the PA/HVA group than in the volunteer group. There was no significant difference in the serum levels of vitamins B2 or B12. These results suggest that low serum concentrations of Vit B6 and iron are involved in PA and HVA. Further studies are needed to clarify the mechanisms involved in such differences.

Neuronal network of panic disorder: the role of the neuropeptide cholecystokinin.

Panic disorder (PD) is characterized by panic attacks, anticipatory anxiety and avoidance behavior. Its pathogenesis is complex and includes both neurobiological and psychological factors. With regard to neurobiological underpinnings, anxiety in humans seems to be mediated through a neuronal network, which involves several distinct brain regions, neuronal circuits and projections as well as neurotransmitters. A large body of evidence suggests that the neuropeptide cholecystokinin (CCK) might be an important modulator of this neuronal network. Key regions of the fear network, such as amygdala, hypothalamus, peraqueductal grey, or cortical regions seem to be connected by CCKergic pathways. CCK interacts with several anxiety-relevant neurotransmitters such as the serotonergic, GABA-ergic and noradrenergic system as well as with endocannabinoids, NPY and NPS. In humans, administration of CCK-4 reliably provokes panic attacks, which can be blocked by antipanic medication. Also, there is some support for a role of the CCK system in the genetic pathomechanism of PD with particularly strong evidence for the CCK gene itself and the CCK-2R (CCKBR) gene. Thus, it is hypothesized that genetic variants in the CCK system might contribute to the biological basis for the postulated CCK dysfunction in the fear network underlying PD. Taken together, a large body of evidence suggests a possible role for the neuropeptide CCK in PD with regard to neuroanatomical circuits, neurotransmitters and genetic factors. This review article proposes an extended hypothetical model for human PD, which integrates preclinical and clinical findings on CCK in addition to existing theories of the pathogenesis of PD.