Cluster headache and oxygen: is it possible to predict which patients will be relieved? A prospective cross-sectional correlation study

Response to 100 % oxygen as acute treatment for cluster headache is relative low considering certain subgroups or predictors. The primary purpose of the present study was to find prospectively which factors differ between responders and non-responders to oxygen therapy. The second goal was to find whether any of these differences would clarify the mechanism of pain reduction by oxygen and cluster headache pathophysiology. Patients diagnosed with cluster headache according to the ICHD-II criteria, who started on oxygen therapy (n = 193), were recruited from 51 outpatient clinics and via patient websites in The Netherlands. Patients had to return two questionnaires around the start of oxygen therapy (n = 120). Eventually, 94 patients were included. Clear non- plus moderate responders had ever used pizotifen more often (p = 0.03). Clear non-responders more often had photophobia or phonophobia during cluster headache attacks (p = 0.047) and more often had used triptans in the same active phase as the phase in which they had used oxygen for the first time (p = 0.02). Using correction for multiple testing, we could only confirm a statistically significant difference in triptan use. We were unable to locate the level of action of oxygen in the thalamus and cortex or confirm the sites of its action presently known, solely based on current knowledge of photophobia circuits. However, we conclude that particularly the higher frequency of photophobia or phonophobia in clear non-responders deserves further study to understand the mechanism of pain reduction by oxygen and cluster headache pathophysiology.     

Rapid maxillary expansion outcomes in treatment of obstructive sleep apnea in children

ObjectivesThe objectives of this study were to confirm the efficacy of rapid maxillary expansion in children with moderate adenotonsillar hypertrophy in a larger sample and to evaluate retrospectively its long-term benefits in a group of children who underwent orthodontic treatment 10 years ago.MethodsAfter general clinical examination and overnight polysomnography, all eligible children underwent cephalometric evaluation and started 12 months of therapy with rapid maxillary expansion. A new polysomnography was performed at the end of treatment (T1). Fourteen children underwent clinical evaluation and Brouilette questionnaire, 10 years after the end of treatment (T2).ResultsForty patients were eligible for recruitment. At T1, 34/40 (85%) patients showed a decrease of apnea–hypopnea index (AHI) greater than 20% (ΔAHI 67.45% ± 25.73%) and were defined responders. Only 6/40 (15%) showed a decrease <20% of AHI at T1 and were defined as non-responders (ΔAHI −53.47% ± 61.57%). Moreover, 57.5% of patients presented residual OSA (AHI > 1 ev/h) after treatment. Disease duration was significantly lower (2.5 ± 1.4 years vs 4.8 ± 1.9 years, p <0.005) and age at disease onset was higher in responder patients compared to non-responders (3.8 ± 1.5 years vs 2.3 ± 1.9 years, p <0.05). Cephalometric variables showed an increase of cranial base angle in non-responder patients (p <0.05).Fourteen children (mean age 17.0 ± 1.9 years) who ended orthodontic treatment 10 years previously showed improvement of Brouilette score.ConclusionStarting an orthodontic treatment as early as symptoms appear is important in order to increase the efficacy of treatment. An integrated therapy is needed.     

Ketamine augmentation rapidly improves depression scores in inpatients with treatment-resistant bipolar depression

Objective: To study the clinical effect of a single ketamine infusion, 0.5?mg/kg body weight, in bipolar depressive patients receiving mood-stabilising drugs, not improving on antidepressants. Previously, in such patients, we had found a correlation between clinical efficacy, serum brain-derived neurotrophic factor and vitamin B12 levels and a rapid improvement in neurocognitive performance.

Methods: The study included 53 patients (13 men, 40 women), aged 22–81 years, receiving ≥1 mood-stabilising medications of the first and/or second generation. Pre-infusion depression intensity on the Hamilton Depression Rating Scale (HDRS) was 23.4?±?4.6 points and the assumed criterion for response was a reduction of ≥50% in the HDRS score after 7 days.

Results: Twenty-seven subjects (51%) met a criterion for response, more frequently males (77%) than females (43%). Responders did not differ from non-responders as to age, illness onset, duration of depressive episode, type of bipolar illness, family history of psychiatric illness, personal/family history of alcoholism or using lithium, quetiapine or a combination of these mood stabilisers.

Conclusions: The results confirm a rapid antidepressant effect of ketamine infusion in a considerable proportion of those patients with bipolar depression receiving mood-stabilising drugs. Apart from male gender, no other clinical factors were predictors of response.     

Effectiveness of low-dose riboflavin as a prophylactic agent in pediatric migraine

BackgroundRiboflavin may prevent migraine episodes; however, there is limited evidence of its effectiveness in pediatric populations. This study investigated the effectiveness of riboflavin and clinical predictors of response in children with migraines.MethodsWe retrospectively reviewed data from 68 Japanese children with migraines, of whom 52 also exhibited another type of headache. Patients received 10 or 40 mg/day of riboflavin. We evaluated the average migraine frequency per month as a baseline and after 3 months of riboflavin therapy to determine the effectiveness and clinical predictors of response.ResultsThe frequency of migraine episodes was significantly lower at 3 months than at baseline (median, [interquartile range], 5.2 (3–7) vs. 4.0 (2–5); p < 0.01). Twenty-five patients (36.7%) showed 50% or greater reduction in episode frequency (responders), while 18 (26.5%) showed a 25%–50% reduction. We compared responders (n = 25) and non-responders (n = 43) and found no significant differences in sex, familial history, riboflavin dose, migraine type (i.e., presence or absence of aura), age at headache onset, or age at consultation. However, non-responders were more likely to have co-morbid non-migraine headaches (odds ratio, 4.11; 95% confidence interval [CI], 1.27–13.33; p = 0.02); this variable was also significant in a multivariate analysis (adjusted odds ratio, 3.8; 95% CI, 1.16–12.6; p = 0.03). Of the co-morbid headache types, only tension headaches were significant (odds ratio, 0.176; 95% CI, 0.04–0.73; p = 0.013). No adverse effects of riboflavin were identified.ConclusionsLow-dose riboflavin is safe and modestly effective for migraines in children. It may be especially beneficial for children without other co-morbid headache types.     

Is 6 months of migraine prophylaxis adequate?

Abstract

Objective:

There is paucity of information on what happens to the migraine attack after withdrawal of prophylactic drugs. In this study we report the outcome of migraine patients after withdrawal of prophylactic medication and also predictors of long-term remission.

Methods:

Migraine patients on prophylactic treatment followed for 1 year were included. Their detailed demographic and clinical information were noted. The patients were followed up at 3, 6, 9, and 12 months. At 6 months, if patients had more than four migraine attacks per month in the last 2 months, they were gradually withdrawn from the treatment. The recurrence of headache during or after withdrawal was noted including its severity, frequency, and the number of analgesic used. The baseline characteristics of the patients with remission and relapse were compared. The predictors of long-term remission were also evaluated.

Results:

One hundred and twenty-seven patients whose median age was 32 years were included. At 6 months withdrawal of prophylactic drug was attempted in 68 patients but was successful in 48 patients only, because 20 relapsed. At 1 year, 70 (63·6%) patients needed prophylactic treatment and drug could be stopped in 40 patients only. The remission was achieved after withdrawal of drug in 48 (43·6%) patients at 6 months, 43 (39·1%) at 9 months, and 40 (36·4%) at 1 year. The most important predictors of persistent remission were improvement at 3 months (P = 0·02) and precipitating factors of migraine (P = 0·005).

Conclusion:

The majority of migraine patients need long-term prophylactic treatment. The patients who respond by 3 months of treatment are more likely to have long-term remission.     

Long-term lithium treatment. Some clinical, psychological and biological aspects

The prophylactic effect of lithium was studied prospectively in 63 patients with recurrent affective disorders. Lithium treatment was started at recovery from a current episode of illness when the patients were able to participate in the decision to start long-term treatment. The median treatment time was 23.7 months and the mean serum lithium concentration approx. 0.63 mmol/l. Comparison with equally long control periods before lithium showed that the treatment resulted in statistically significant reductions in number of episodes, number of months ill, and number of months hospitalized. There were 40 (63%) responders (frequency of episodes during lithium lower than before lithium) and 23 (37%) non-responders (frequency of episodes during lithium higher than or the same as before lithium). Females responded slightly better than males. Responders scored significantly higher than non-responders in the psychasthenia and muscle tension subscales of the Karolinska Hospital Personality Inventory. Both responders and non-responders showed falls in CPRS during lithium treatment, the fall was statistically significant in the responders. During the first 4 months of lithium treatment the responders showed a significant rise in serum calcium, while serum calcium remained unaltered in the non-responders. These variables may be predictive of response to long-term lithium treatment. The low numbers of patients who discontinued treatment and the even serum levels of lithium suggest that good compliance to treatment was achieved with the present approach.     

Responders to rTMS for depression show increased fronto-midline theta and theta connectivity compared to non-responders

Background

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, but only some individuals respond. Predicting response could reduce patient and clinical burden. Neural activity related to working memory (WM) has been related to mood improvements, so may represent a biomarker for response prediction.

Brain functional effects of electroconvulsive therapy during emotional processing in major depressive disorder

BackgroundIn treatment-resistant major depressive disorder (MDD), electroconvulsive therapy (ECT) is a treatment with high efficacy. While knowledge regarding changes in brain structure following ECT is growing, the effects of ECT on brain function during emotional processing are largely unknown.ObjectiveWe investigated the effects of ECT on the activity of the anterior cingulate cortex (ACC) and amygdala during negative emotional stimuli processing and its association with clinical response.MethodsIn this non-randomized longitudinal study, patients with MDD (n = 37) were assessed before and after treatment with ECT. Healthy controls (n = 37) were matched regarding age and gender. Functional magnetic resonance imaging (fMRI) was obtained twice, at baseline and after six weeks using a supraliminal face-matching paradigm. In order to evaluate effects of clinical response, additional post-hoc analyses were performed comparing responders to non-responders.ResultsAfter ECT, patients with MDD showed a statistically significant increase in ACC activity during processing of negative emotional stimuli (p_FWE = .039). This effect was driven by responders (p_FWE = .023), while non-responders showed no increase. Responders also had lower pre-treatment ACC activity compared to non-responders (p_FWE = .025). No significant effects in the amygdala could be observed.ConclusionsECT leads to brain functional changes in the ACC, a relevant region for emotional regulation during processing of negative stimuli. Furthermore, baseline ACC activity might serve as a biomarker for treatment response. Findings are in accordance with recent studies highlighting properties of pre-treatment ACC to be associated with general antidepressive treatment response.     

Decreased chemosensitivity and improvement of sleep apnea by nocturnal hemodialysis

Background:Sleep apnea occurs in up to 50% of patients with end-stage renal disease and is improved by nocturnal hemodialysis. We hypothesized that its pathogenesis is related to changes in chemoreflex responsiveness.Methods:Twenty-four patients receiving conventional hemodialysis (4 h/day, 3 times/week) had overnight polysomnography and measurement of the ventilatory response to carbon dioxide during isoxic hypoxia and hyperoxia using a modified rebreathing technique. Measurements were repeated following conversion from conventional to nocturnal hemodialysis (8 h/night, 3–6 nights/week). Patients were divided into apneic and non-apneic groups based on apnea–hypopnea index ?15/h at baseline (17 apneics and 7 non-apneics), and the apneic group was further divided into “responders” and “non-responders” based on a significant reduction in AHI at follow-up.Results:Conversion from conventional to nocturnal hemodialysis was associated with a decrease in the ventilatory sensitivity to hypercapnia during hyperoxia in responders (3.2 ± 1.0 vs. 2.3 ± 1.3 L/min/mmHg) but not in non-responders (2.8 ± 1.3 vs. 2.9 ± 1.6 L/min/mmHg). The change in ventilatory sensitivity was correlated with the change in apnea–hypopnea index in all apneic patients (r = .528, p = 0.029).Conclusions:Improvement of sleep apnea following conversion from conventional to nocturnal hemodialysis is associated with a decrease in chemoreflex responsiveness. This finding suggests that increased chemoreflex responsiveness contributes to the pathogenesis of sleep apnea in some patients with end-stage renal disease.     

Predictive value of heart rate in treatment of major depression with ketamine in two controlled trials

ObjectiveKetamine has been shown to be effective in treatment of episodes of major depressive disorder (MDD). This controlled study aimed to analyse the predictive and discriminative power of heart rate (HR) and heart rate variability (HRV) for ketamine treatment in MDD.MethodsIn 51 patients, HR and HRV were assessed at baseline before and during ketamine infusion and 24 hours post ketamine infusion. Montgomery–Åsberg Depression Rating Scale (MADRS) was used to assess changes of depressive symptoms. A 30% or 50% reduction of symptoms after 24 hours or within 7 days was defined as response. A linear mixed model was used for analysis.ResultsKetamine infusion increased HR and HRV power during and after infusion. Responders to ketamine showed a higher HR during the whole course of investigation, including at baseline with medium effect sizes (Cohen’s d = 0.47–0.67). Furthermore, HR and HRV power discriminated between responders and non-responders, while normalized low and high frequencies did not.ConclusionThe findings show a predictive value of HR and HRV power for ketamine treatment. This further underlines the importance of the autonomous nervous system (ANS) and its possible malfunctions in MDD.SignificanceThe predictive power of HR and HRV markers should be studied in prospective studies. Neurophysiological markers could improve treatment for MDD via optimizing the choice of treatments.     

Thalamic Deep Brain Stimulation May Improve Restless Legs Syndrome in Patients With Essential Tremor

ObjectivesTo determine change in restless legs syndrome (RLS) symptoms in essential tremor (ET) patients undergoing bilateral thalamic ventral intermedius (VIM) deep brain stimulation (DBS) surgery.Materials and MethodsWe retrospectively reviewed our database of ET patients with RLS who had undergone VIM DBS for tremor from 2012 to 2020. We reviewed the patients with available International Restless Leg Syndrome Study Group RLS scale scores before and after DBS. Percentage of responders, defined as proportion of patients experiencing three or more point improvement of RLS scores post-DBS, was calculated. We performed two-tailed t-test of pre-DBS and post-DBS RLS scores.ResultsWe identified 13 patients with ET and RLS who had undergone bilateral VIM DBS, of whom nine (69%) were responders post-DBS. Five of 13 patients (38%) had complete resolution of RLS post-DBS. For all patients, mean pre-DBS RLS score was 15.8 ± 7.9 which improved by 46% post-DBS to a mean of 8.5 ± 8.8 (p = 0.007). Four patients rated their RLS scale one night with the stimulator OFF and another night with the stimulator ON. The mean RLS score with stimulator ON was 15.5 ± 7.6 which improved by 53% to a mean of 6.25 ± 7.8 (p = 0.008), with two having complete resolution of RLS with stimulator ON. Of the nine responders, six preferred to keep their stimulator ON at night due to relief of RLS and better subjective quality of sleep.ConclusionsWe report for the first time improvement of RLS in patients with ET after bilateral thalamic DBS. Although many ET patients with nonrechargeable DBS systems switch off their stimulator at night to conserve battery life, those with RLS may potentially benefit from keeping their stimulator ON at night to relieve their RLS.     

Clinical features and outcomes of spinal cord infarction following vertebral artery dissection: a systematic review of the literature

Abstract

Objective: Spinal cord infarction (SCI) is a rare complication of vertebral artery dissection (VAD). Its clinical features and outcomes have not yet been well documented.

Methods: In addition to reporting a case with bilateral SCI caused by left VAD, we performed a systematic review of the literature conducted through a PubMed search.

Results: A total of 17 cases were reviewed (nine men and eight women). The average age was 40·5±14·6 years. In addition to neck pain or headache (88%), patients with VAD-associated SCI often presented with a sensory level (76%) or Brown–Séquard syndrome (53%). The most common regions of dissection were at the V1 or proximal V2 segments, and the infarcted area of SCI was mainly located at C2–C5 levels. Regarding the vascular territory, posterior spinal artery infarction was noted in 29% of patients, spinal sulcal artery infarction in 42%, and anterior spinal artery (ASA) watershed infarction in 29%. Eleven patients (65%) had a good outcome and six patients (35%) had a poor outcome (including one mortality; 6%). Smoking, age above 50 years, and ASA watershed infarction were associated with a poor outcome, while spinal sulcal artery infarction was associated with a good outcome.

Conclusion: Neck pain or headache is an important warning symptom of VAD, and the presence of a concomitant sensory level or Brown–Séquard syndrome is helpful for the early diagnosis of SCI caused by VAD. One-third of patients had a poor outcome, and smoking, old age, and ASA watershed infarction represented important risk factors.     

High frequency repetitive transcranial magnetic stimulation (rTMS) is effective in migraine prophylaxis: an open labeled study

Abstract

Objective: To evaluate the effect of high rate repetitive transcranial magnetic stimulation (rTMS) in migraine prophylaxis in medically refractory patients.

Methods: Migraine patients above 15 years of age, having more than 7 attacks/month and refractory to at least two prophylactic drugs were included. The patients were evaluated for migraine frequency, severity, functional disability, number of rescue medications and migraine index. Three sessions of alternate day 10 Hz rTMS comprising of 600 pulses in 10 trains were delivered to left frontal cortex. The response was evaluated at the end of session and weekly for 4 weeks.

Results: Fifty-one patients aged 16–61 years and 45 females were treated. Fifty (98%) patients had more than 50% reduction of headache frequency at the end and 1 week after rTMS and the improvement persisted till the fourth week in 80·4% patients. The headache frequency, severity, functional disability, migraine index, and rescue medications significantly reduced at all time points, but the maximum benefit was observed in the first 2 weeks. There were no serious adverse events.

Conclusion: High rate rTMS in left frontal cortex is effective and well tolerated for migraine prophylaxis.     

Caudate volume differences among treatment responders,non-responders and controls in children with obsessive–compulsive disorder

Treatment response in obsessive–compulsive disorder (OCD) is heterogeneous and the neurobiological underpinnings of such variability are unknown. To investigate this issue, we looked for differences in brain structures possibly associated with treatment response in children with OCD. 29 children with OCD (7–17 years) and 28 age-matched controls underwent structural magnetic resonance imaging. Patients then received treatment with fluoxetine or group cognitive-behavioral therapy during 14 weeks, and were classified as treatment responders or non-responders. The caudate nucleus, thalamus and orbitofrontal cortex were selected a priori, according to previous evidence of their association with OCD and its treatment. Gray matter (GM) volume comparisons between responders, non-responders and controls were performed, controlling for total GM volume. 17 patients were classified as responders. Differences among responders, non-responders and controls were found in both caudate nuclei (both p-values = 0.041), but after Bonferroni correction for multiple comparisons, these findings were non-significant. However, after excluding the effect of an outlier, findings were significant for the right caudate (p = 0.004). Pairwise comparisons showed larger caudate GM volume in responders versus non-responders and controls, bilaterally. The right caudate accounted for 20.2% of the variance in Y-BOCS changes after treatment in a linear regression model, with a positive correlation (p = 0.016). We present a possible neural substrate for treatment response in pediatric OCD, which is in line with previous evidence regarding the caudate nucleus. Considering the limitations, further research is needed to replicate this finding and elucidate the heterogeneity of treatment response in children with OCD (National Clinical Trials Registration Number: NCT01148316).

     

Optical coherence tomography angiography findings of multiple sclerosis with or without optic neuritis

ABSTRACT

Objective: Nowadays, retinal microvascular structures can be investigated using optical coherence tomography angiography (OCTA). We aimed to evaluate the probable vascular changes in the foveal and peripapillary regions of patients with multiple sclerosis (MS).

Methods: A total of 20 patients with relapsing remitting multiple sclerosis (RRMS) and 24 healthy controls were recruited in this study. All participants’ superficial and deeper retinal and peripapillary layers were evaluated using OCTA after a total ophthalmologic examination.

Results: In the superficial plexus, the whole image (49.53 ± 3.9% and 51.83 ± 2.1%, p = 0.009), superior hemisphere (49.44 ± 4.11% and 51.63 ± 2.3%, p = 0.018), inferior hemisphere (49.75 ± 3.9% and 52.03 ± 2.2%, p = 0.012), parafoveal (51.87 ± 3.9% and 53.08 ± 3.46%, p = 0.048) and perifoveal (50.41 ± 3.86% and 52.76 ± 2.1%, p = 0.007) vascular densities were statistically significant lesser in patients with RRMS than in controls. In the optic disc OCTA parameters, the vessel density of the inferior (50.15 ± 6.99% and 53.04 ± 3.63% p = 0.043) and temporal sector (48.09 ± 5.47% and 50.85 ± 5.24%, p = 0.045) were statistically significantly lesser in patients with RRMS than in controls.

Conclusion: The reductions in vessel density of the retinal or peripapillary area of patients with RRMS shown in this study should be investigated further to determine whether it is a secondary lesion to optic neuritis (ON) or a primary vasculopathic condition of MS.     

Novel Definition of Stroke “Good Responders” Predicts 90-Day Outcome after Thrombolysis

IntroductionIdentifying predictors of good response in thrombolytic-treated stroke is important to clinical care, resource allocation, and research design. We developed a simple, novel measure of “Good Responders” to assess if 2 short-term variables could predict 90-day outcomes after thrombolysis in stroke.MethodsIntravenous thrombolysis-treated stroke cases from June 2004 to June 2018 were analyzed from a stroke registry. Intraarterial treatment cases were excluded. Good responders (GR++) were defined as those with length of stay less than or equal to 3 days and discharge to home. Poor responders (GR- -) had length of stay more than 3 days and discharge other than home. Mixed responders (GR+/-) composed the remainder. Baseline characteristics and predictors of 90-day outcome were assessed.ResultsOf 261 patients, there were 101(38.7%) GR++, 67(25.7%) GR- -, and 93(35.6%) GR+/-. For GR++ versus GR- - versus GR+/-, there were differences in mean age (62.7, 71.2, 69.2; P = .0016), and baseline modified Rankin score (mRS) 0-2 (%: 94.9, 74.6, 84.8; P = .008). Younger age, male sex, lower values for systolic BP, glucose, and baseline mRS were associated with good responders. Older age, atrial fibrillation, symptomatic intracerebral hemorrhage, and baseline mRS greater than 2 were associated with poor responders. At 90 days, mortality was reduced in GR++ versus GR- - versus GR+/- (%alive: 92.6, 72, 86; P = .04), and mRS(0-2) (%: 36.8, 0, 11.8; P < .001).ConclusionsGood responders to thrombolysis are younger and have better baseline functional status. Our novel definition of “Good Responders”, using 2 early variables of home disposition and short length of stay, may help predict 90-day post-thrombolytic outcome. Future work should focus on validating this definition.     

The change of QEEG prefrontal cordance as a response predictor to antidepressive intervention in bipolar depression. A pilot study

ObjectivesThe aim of the study was to examine whether the change of quantitative EEG (QEEG) theta prefrontal cordance after one week of various antidepressive interventions predicts response to a 4-week treatment in patients with bipolar depression.MethodsWe investigated 20 inpatients who completed a 4-week treatment. EEG data were monitored at baseline and after 1 week of treatment. QEEG cordance was computed at 3 frontal electrodes (Fp1, Fp2, Fz) in theta frequency band. Depressive symptoms and clinical status were assessed using Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression (CGI) and Young Mania Rating Scale (YMRS).ResultsSeven of 8 responders (reduction of MADRS ≥50%) and only 2 of 12 non-responders had decreased prefrontal theta cordance value after the first week of treatment (p = 0.02). The positive and negative predictive values of cordance reduction for response were 0.78 and 0.91, respectively. We also found significant differences in cordance value reductions between responders and non-responders after week 1 and higher baseline cordance in responders. Conclusion: The change in prefrontal theta cordance was associated with subsequent change in depressive symptoms and potentially might be a useful tool in the early detection of acute response to antidepressive interventions in bipolar depressed patients.     

Association study of paroxetine therapeutic response with SERT gene polymorphisms in patients with major depressive disorder.

We investigated the relationships between LS promoter (SERTPR) and ls intron2 (SERTin2) genetic variants of serotonin transporter (SERT) polymorphisms with treatment response in 130 patients with major depressive disorder (MDD) treated with paroxetine (20 mg/day) for 6 weeks. To assess and evaluate therapeutic response to paroxetine all patients were rated weekly using the HAMD-17 scale. Responders were defined as those subjects with a decrease in HAMD scale by>/=50% at week 6 of treatment. Comparison of genotypes and alleles frequency of the SERTPR between responders and non-responders revealed significant differences among genotypes and overrepresentation of the S allele in the group of non-responders (P=0.0004). SERTin2-ss genotype bearing subjects showed better treatment response compared to ls and ll genotype from the fourth week of treatment (P=0.035). Statistical differences were also found in distributions of the estimated haplotypes between responders and non-responders, while subsequent analysis revealed overrepresentation of S/l haplotype (P=0.006) in the group of non-responders. SERTPR and SERTin2 were found to be in linkage disequilibrium in studied population. These findings identify genetic factors associated with paroxetine treatment response in MDD patients.     

Patient characteristics predicting responses to intravenous ferric carboxymaltose treatment of restless legs syndrome

BackgroundSignificant benefit of intravenous ferric carboxymaltose (FCM) treatment for restless legs syndrome (RLS) has been well-established. However, no clinical indicators predicting treatment response of RLS have been established. This study aimed to determine factors predicting outcome of clinical FCM treatment of RLS patients.MethodsData were retrospectively reviewed from all patients who received FCM treatment for RLS from April 2016 to April 2019. These data included: detailed history, international RLS scale score (IRLS), questionnaires, comorbidity, and previous RLS medication use. Morning fasting serum iron, ferritin, and total iron-binding capacity were measured before and at four weeks after treatment. RLS patients with possible secondary RLS were identified by reviewing the medical histories. This included patients with iron deficiency anemia, lumbosacral radiculopathy, and gastrectomy. Primary RLS included those with no indication of secondary medical factors contributing to RLS. Treatment response was assessed using the IRLS and clinical ratings at four weeks after FCM administration. Patients with a greater than 40% decrease in IRLS were classified as responders.ResultsThe study comprised 164 patients with IRLS and clinical ratings obtained before and at four weeks after intravenous (IV) iron. Treatment responses differed considerably between diagnostic groups of RLS. Percentage responding was: 64.7% (66 of 102) for patients with primary RLS, 90.9% (10 of 11) with gastrectomy, 91.3% (21 of 23) with iron deficiency anemia and 39.3% (11 of 28) with lumbosacral radiculopathy. When responders were compared to non-responders in primary RLS patients, responders had significantly lower serum iron (80.5 ± 26.7 vs. 95.8 ± 30.5 μg/dL, p = 0.022) and percentage transferrin saturation (%TSAT) (25.4 ± 9.6 vs. 30.5 ± 10.5%, p = 0.026) in females, but not males. Logistic regression controlling for major subject variables showed that %TSAT significantly predicted response. (odds ratio [OR]: 0.955, confidence interval: 0.913–0.998, p = 0.040).ConclusionIntravenous FCM in moderate to severe RLS patients is beneficial as a first-line or add-on treatment, particularly for patients with compromised peripheral iron state. Overall, lower %TSAT predicted better chance of responding to the IV iron treatment especially for females.