objective is to assess feasibility, tolerability and efficacy of aiTBS in patients with bipolar depression (BPD) and negative symptoms of schizophrenia (NSS).
ID
Source
Brief title
Condition
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcomes are response (defined by 50% reduction on the HDRS, QIDS-SR ,
PANSS, SANS and CDSS), remission (defined by HDRS <7, QIDS-SR <5, all items on
the negative scale PANSS <3, SANS <3, CDSS<6) and feasibility and tolerability
measured by side-effects and drop-out rates.
Secondary outcome
To assess Heart Rate Variability (HRV) as part of parasympatic activation
through dlPFC stimulation. HRV is measured through electrocardiogram (ECG).
Background summary
Repetitive Transcranial Magnetic Stimulation (rTMS) is an emerging non-invasive
technique of neuromodulation. rTMS is an approved, evidence-based and safe
treatment modality for major depressive disorder (MDD). Recent studies have
proposed new adaptations of TMS, one adaptation being accelerated intermittent
theta-burst stimulation (aiTBS). A case series of 6 patients (4 MDD and 2 BPD)
found high response and remission rates following the treatment of an
accelerated form of iTBS (using the Stanford Neuromodulation Therapy (SNT)
protocol). Response and remission rates were 83.5% and respectively 66.7%. The
treatment was found to be safe and tolerable. A-proof-of concept study in 2020
conducted by the same research group found that aiTBS using the same protocol
protocol in 21 patients (19 MDD and 2 BPD) was highly effective; response and
remission rates were 90.5% following the SNT protocol. The study also showed
feasibility and tolerability. Following this pilot study, a double blind RCT in
2021 found that 85.7% of patients with MDD in the active STN protocol met
response criteria and 78.6% met remission criteria over a 4-week follow-up
period. These response and remission rates are much higher than currently
approved rTMS protocols for TRD (approximately 25-65%). The question arises
whether aiTBS shows efficacy in other psychiatric disorders including bipolar
depression (BPD) and negative symptoms of schizophrenia (NSS).
Study objective
objective is to assess feasibility, tolerability and efficacy of aiTBS in
patients with bipolar depression (BPD) and negative symptoms of schizophrenia
(NSS).
Study design
Proof-of-concept study with an open-label design. 2 groups will be included,
namely patients with BPD and patients with NSS. Both groups will be treated
according the aiTBS-5d-8s-50i protocol in which patients are treated for 5
consecutive days with 8 daily aiTBS with a 50 minute intersession interval.
Questionnaires (HDRS, QIDS-SR, PANSS, SANS and CDSS) will be measured daily and
during follow-up (2 weeks, 4 weeks, 12 weeks) to assess response.
Intervention
aiTBS according to aiTBS-5d-8s-50i protocol (5 consecutive days, 8 daily
session, 10 minutes of stimulation with 50 minute interval).
Study burden and risks
the burden and risks associated with participation are considered minimal.
Associated risks with stimulation are low in the studies published regarding
aiTBS. The side effects of aiTBS are similar to rTMS, an already safe and
tolerable treatment modality. These side effects of aiTBS are mild, short term
and transient and include fatigue, some discomfort at stimulation site, neck
pain, headache and dizziness. Most of these side effects occur during or
shortly after the first session and tend to rapidly decrease after the first
session. The most severe adverse events is induction of an epileptic seizure.
Regarding aiTBS, the limited studies available (3 studies, n=56) did not report
serious adverse events. In iTBS, only 1 case reported on a seizure following
iTBS. In case of a seizure, the prevalence in rTMS is found to be 1 of 60000
sessions and almost nihil if a patient is free of medication or free of
co-morbid neurological disorders. In iTBS, only 1 case report reported on a
seizure following iTBS. To reduce risk of a seizure, participants with a higher
risk (a history of epilepsy or first degree relative with epilepsy) are
excluded from the study. Since aiTBS is similar to rTMS and iTBS, the same
adverse events are to be expected. Therefore, the risk administering aiTBS is
expected to be minimal.
A review on rTMS (Xia et al., 2008) reported the prevalence of an affective
switch to hypomania/mania to be 0.84% in the active rTMS compared to 0.73% in
the sham group (non-significant difference). Several case reports have
described an affective switch in major depressive disorder following rTMS,
however according to recent evidence-based guidelines, there is currently no
evidence to suggest rTMS is associated with an increased risk of an affective
switch to hypomania or mania. A meta-analysis in 2016 (Gold et al.,) suggests
that rTMS is safe in case of BPD with a very low risk of induction of an
affective switch (1/106 in active group and 1/75 in sham group). 3 relevant
randomized controlled trials of iTBS in patients with negative symptoms of
schizophrenia, did not find a worsening in positive symptoms after iTBS.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- 18-65 years
- Ability to freely written informed consent
- DSM-5 diagnosis of current depressive episode in bipolar I or II disorder OR
DSM-5 diagnosis of schizophrenia
- Therapy resistanve in bipolar disorder
- HDRS>16 in bipolar depression at start study
- SANS>3 on each item in schziphrenia
- Stable medication (antidepressants or antipsychotics) at least 4 weeks prior
start study.
Exclusion criteria
* In BPD, (hypo) manic episode within 3 months prior start of the trial;
* In BPD, Young Mania Rating Scale (YMRS) score of >12 prior start of the trial;
* Patients with bipolar II disorder who use anti-depressant medication without
anti-manic medication or patients with bipolar I disorder, not using anti-manic
medication;
* Acute suicidality;
* (History of) neurological disease
* (History of) epilepsy or epilepsy in a 1st degree relative;
* Pregnancy;
* Disorder in substance abuse
* Known serious somatic health problem;
* Used recreational drugs over a period of 72 hours prior each session;
* Used alcohol within the last 24 hours prior each session;
* Specific TMS contraindications (see standard screening form, appendix 1):
ICD, pacemaker, history of epileptic seizures of epilepsy in a 1st degree
relative, intracranial metal implants(e.g. cochlear implant or deep brain
stimulator).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83361.018.22 |