Nathalie Vanderbruggen

Intensive HF-rTMS treatment in refractory medication-resistant unipolar depressed patients.

BACKGROUND Major depression is a worldwide severe mental health problem. Unfortunately, not all depressed patients respond to pharmacotherapy or psychotherapy, even when adhering to treatment guidelines. Even though current guidelines do not in particular advocate repetitive Transcranial Magnetic Stimulation (rTMS) in refractory treatment resistant depression (TRD), using more intensive stimulation parameters might hold promise as a valuable alternative. OBJECTIVE Consequently, in this randomized sham-controlled crossover study, we wanted to evaluate clinical outcome of intensive HF-rTMS treatment in TRD when applied to the left dorsolateral prefrontal cortex (DLPFC). METHODS After a 2-week antidepressant washout, 20 unipolar TRD patients, at least stage III, received 20 sham-controlled high-frequency (HF)-rTMS sessions, in a crossover design. Five daily suprathreshold HF-rTMS sessions were spread over four successive days delivering in total 31,200 stimuli. RESULTS Overall, the procedure resulted in immediate statistical significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham), suggesting possible placebo responses. On the other hand, albeit only 35% (7/20) of the patients showed a 50% reduction of their initial Hamilton Depression rating score at the end of the two-week procedure, all these patients showed a prompt clinical response after real HF-rTMS treatment, not after sham. Furthermore, a shorter duration of the current depressive episode was a predictor for beneficial clinical outcome. Unresponsiveness to former ECT could be indicative for negative clinical outcome in these kinds of patients. LIMITATIONS Single center setup with relatively small sample size and no follow-up. CONCLUSIONS Our findings indicate that intensive HF-rTMS treatment might have the potential to result in fast clinical response when confronted with a refractory TRD patient.

Intensive high-frequency repetitive transcranial magnetic stimulation treatment in an electroconvulsive shock therapy-resistant bipolar I patient with mixed episode

This case report describes a 52-year-old woman who received a diagnosis of bipolar I disorder of the mixed type, resistant to bilateral electroconvulsive shock therapy (ECT) and successfully treated with intensive left-sided high frequency repetitive transcranial magnetic stimulation (HF-rTMS).

Pseudomalabsorption of Levothyroxine: A Challenge for the Endocrinologist in the Treatment of Hypothyroidism

Background: Hypothyroidism due to non-compliance with levothyroxine therapy (pseudomalabsorption) is rare. The diagnosis is considered in patients with persistent severe hypothyroidism despite treatment with large doses of levothyroxine. Intestinal malabsorption, drug and dietary interference with levothyroxine absorption and nephrotic syndrome should be excluded. The diagnosis of pseudomalabsorption can be demonstrated by using “an oral 1,000 µg of levothyroxine test” showing a rapid decrease in thyroid-stimulating hormone and increase in thyroxine. There are however few data on the sensitivity and specificity of the test in large cohorts of hypothyroid patients. Treatment of pseudomalabsorption is controversial, with reports using parenteral, intramuscular or single weekly oral dosing of levothyroxine. Cases: We report 3 patients who presented with persistent clinical and biochemical signs of hypothyroidism despite replacement therapy with high doses of levothyroxine. Pseudomalabsorption was diagnosed by a systematic approach, including prior exclusion of digestive, liver and kidney diseases. A peroral challenge test was positive in all cases. Patients denied non-compliance, and a psychiatric approach was elusive. Two of the patients were treated successfully with a single supervised weekly 1,000-µg administration of levothyroxine, while non-supervised weekly administration resulted in hypothyroidism confirming pseudomalabsorption. Conclusions: Non-compliance with medical therapy should be considered in patients with treatment-refractory hypothyroidism. Supervised once weekly levothyroxine treatment is a safe and well-tolerated treatment option, obviating the need for parenteral administration of the drug. Apart from the medical treatment, there is also a need for psychiatric evaluation and care.

Intensive HF-rTMS treatment in an ECT resistant bipolar I patient with mixed episode

Although electroconvulsive shock therapy (ECT) remains a successful treatment strategy in medication-resistant bipolar disorder, not all patients respond well. Here, we report on a successful high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) therapy in a highly treatment-resistant bipolar I patient during a mixed episode. This case illustrates that “combative” HF-rTMS therapy could be a safe and valid treatment alternative for refractory bipolar I patients with mixed episodes.

Stijging in de prevalentie van autismespectrumstoornissen: feit of fictie?

Autisme is een ontwikkelingsstoornis die zich kenmerkt door tekortkomingen op het vlak van communicatie en sociale interactie, alsook door de aanwezigheid van beperkte en zich herhalende, stereotiepe patronen van gedrag en/of interesses. Een recente toename in het diagnosticeren van autismespectrumstoornissen (ASS) bij volwassenen brengt deze problematiek onder de aandacht. Mogelijke verklaringen en hypothesen voor de vastgestelde stijging in prevalentie worden toegelicht aan de hand van een literatuurstudie.

P02-08 - The influence of treatment-resistance on the serotonin 2A receptor in unipolar melancholic depression

Introduction Major depression is one of the most common mental diseases, and quite a number of patients are resistant to several psychopharmacological interventions, even when applying current treatment guidelines. To date, it remains unclear as to how the serotonergic system is implicated in treatment-resistance found in melancholically depressed patients. Objectives & aims In this study, we examined the involvement of post-synaptic 5-HT2A receptors in the pathophysiology of treatment resistance in major depression with 123I-5-I-R91150 SPECT, focusing on the frontal cortex and hippocampus. Method 15 unipolar antidepressant naive (ADN) patients and 15 treatment-resistant depressed (TRD) patients, all of the melancholic subtype, matched for age and gender were studied. All subjects were antidepressant free when they underwent a static 123I-5-I-R91150 SPECT scan. Results Compared to ADN patients, TRD patients displayed significantly less 5-HT2A receptor binding index (BI) in the dorsal regions of the prefrontal cortex and in the anterior cingulate cortex. No hippocampal 5-HT2A receptor BI differences were observed. Conclusions Our results suggest that when confronted with treatment resistance in melancholic depression the 5-HT2A receptors in the DPFC-ACC axis are significantly more down-regulated when compared to depressed ADN patients. This might to some extent explain the observed continued cognitive problems and might reflect the long-term serotonin depletion with reduced neurogenesis in treatment resistant patients.

P02-537 - The Effect of One Left-Sided Preferontal HF-rTMS Session on Emotional Brain Processes

Introduction Although repetitive Transcranial Magnetic Stimulation (rTMS) is frequently used to examine emotional changes in healthy volunteers, it remains largely unknown how rTMS is able to influence emotion. Objectives, aims & methods In this sham-controlled single-blind crossover study using fMRI, we examined in 20 right-handed healthy female volunteers whether a single high frequency (HF)-rTMS session applied to the left dorsolateral prefrontal cortex (DLPFC) could influence emotional processing while focussing on blocks of positively and negatively valenced baby faces. The task instruction was to focus on ones own emotional status elicited by the visual stimuli. Results A single HF-rTMS session selectively influenced the processing of positively and negatively valenced baby faces. When positive information was being processed, one active left-sided HF-rTMS session resulted in enhanced neuronal activity in the left superior frontal cortex (Brodmann area 10) and right inferior parietal cortex (Brodmann area 39). When negative information was processed, one active stimulation session attenuated neuronal activity in the right insula, while sham stimulation did not. Discussion These observations suggest that after one active HF-rTMS session, psychophysiological reactions while processing withdrawal-related stimuli decrease. The increased neuronal activity while processing of positively valenced baby faces might reflect enhanced task-related processing caused by the neuronal activation of the left DLPFC, which could indicate that females are more able to empathize with the depicted happy baby faces. Our results add further evidence as to why HF-rTMS applied to the left DLPFC might improve mood in depressive populations.

Acute Relapse After Successful Vagus Nerve Stimulation Therapy: A Case Report of Last-Resort ECT Treatment

To the Editor: Quite a number of patients suffering from major depression are resistant to several psychopharmacologic interventions, even when current treatment guidelines are applied.1,2 Electroconvulsive therapy (ECT) is considered a valid alternative treatment option with established efficacy in treatment-resistant depression (TRD),3 yielding response rates of up to 60%.4 When ECT nonresponse is confronted, treatment options are limited.5 In these cases, vagus nerve stimulation (VNS) has been proposed as a continuous antidepressant strategy.6–8 However, when patients who have achieved remission with VNS relapse, guidelines are absent. Case report. Mr A, a 64-year-old male patient, had a history of recurrent unipolar depressed episodes since 1990 (per DSM-IV-TR criteria and ICD-9-CM code 296.34). According to the Thase and Rush staging system for TRD (from 0 to 5), the patient was considered maximally treatment resistant, as multiple trials of psychopharmacologic agents and several adequately performed bilateral ECT applications were unsuccessful.9 At the end of 2004, it was decided to implement VNS. After titration of the VNS parameters (intensity: 1.25 mA, frequency: 20 Hz, pulse width: 500 ms, signal on time: 30 sec, signal off time: 3 min), the patient achieved complete remission after 1 year, and euthymia was sustained for another 2 years. Concomitant pharmacotherapy was venlafaxine 225 mg/d and mirtazapine 30 mg/d. During the spring of 2008, the patient unexpectedly relapsed. Because of the presence of severe psychotic features with suicidal risk and to avoid cognitive side effects, we decided to acutely treat the patient with unilateral ECT. After 11 sessions, the patient reached euthymia (parameters: 1.0 ms, 60 Hz, 3.00 s, 0.8 mA, and 288 mC during sessions 1 to 5; 1.0 ms, 70 Hz, 3.00 s, 0.8 mA, and 336 mC during sessions 6 to 8; and 1.0 ms, 70 Hz, 3.50 s, 0.8 mA, and 392 mC during sessions 9 to 11, for a total convulsion time of 333 s). This clinical remission was confirmed with a score of 0 on the 21-item Beck Depression Inventory (BDI)10 and a score of 5 on the 17-item Hamilton Depression Rating Scale (HDRS).11 Only during the administration of ECT was the VNS device turned off. After ECT was administered, we changed the VNS intensity to 1.50 mA and added olanzapine 10 mg/d to the ongoing treatment with mirtazapine and venlafaxine. With this treatment combination, the patient remains in full remission: BDI = 0, HDRS = 5 after 6 months and BDI = 4, HDRS = 6 after 1 year. Although ECT is considered the “gold standard” for efficacy in TRD, not all patients respond and further treatment options are limited. In addition, ECT relapse rates remain high, and relapse generally occurs in the first 6 months.12 Relapse rates during VNS therapy are not yet established.8,13 Husain and colleagues14 reported a similar case of relapse during VNS therapy in a female patient with TRD. Although remission was achieved with bilateral ECT, long-term efficacy data were not provided. In short, besides the fact that the concomitant use of ECT with VNS was found to be safe,15,16 our case indicates that, when severe relapses occur in patients previously treated successfully with VNS, ECT, even when previously associated with only moderate response, can be performed effectively with good long-term clinical outcome results.

P02-77 Can salivary cortisol assessment from a single HF-rTMS session predict clinical outcome in melancholic depressed patients? A pilot study

Aim The underlying physiological mechanisms as to why repetitive transcranial magnetic stimulation (rTMS) can treat depressed patients remains unclear and no clear biological markers are available to indicate a positive outcome for a given patient. Some data suggest that rTMS can influence hypothalamic-pituitary-adrenal (HPA) processes. In this study, we wanted to evaluate whether one session of high frequency (HF)-rTMS applied on the left dorsolateral prefrontal cortex (DLPFC) can predict a successful treatment outcome in a sample of antidepressant free unipolar depressed patients of the melancholic subtype. Methods Twenty one right-handed treatment resistant depressed patients were studied. Fifty two percent of the patients were considered as treatment responders, as defined by a 50% reduction in her/his baseline 17-item Hamilton Depression Rating Scale (HDRS) score. To examine acute HF-rTMS effects on the HPA- axis, we analyzed salivary cortisol levels, using a sham-controlled, ‘single’ blind, crossover design. Areas under the curves (AUC) were calculated for both real and sham HF-rTMS. Results Real HF-rTMS resulted in salivary cortisol decreases, however only in HF-rTMS non-responders. No HF-rTMS influences were found in the responder group. Sham stimulation did not affect the HPA-axis. Non-responders were found to display a higher level of co-morbid personality disorders. Conclusion Our results may provide more insight into the underlying working mechanisms of HF-rTMS and could add further information about endocrinological functioning in affective disorders. Furthermore, personality features in combination with a ‘super-sensitive’ HPA system could be of importance to predict clinical outcome.