Key Takeaways

From the Authors As published in the article
  1. Effective treatments for persistent negative symptoms in schizophrenia are limited, and previous intermittent theta burst stimulation (iTBS) studies have been inconsistent. This study explores whether left dorsolateral prefrontal cortex iTBS helps patients with chronic, treatment-resistant symptoms.
  2. Practitioners should recognize that iTBS may not provide meaningful benefit for longstanding or primary negative symptoms, particularly with stable medication and limited neuroplasticity.
  3. When using neuromodulation, patient characteristics, treatment duration, and protocol are important considerations. Some patients may need longer, tailored courses or alternative strategies if standard iTBS does not work.
Extended Takeaways
  1. This trial tested a nonstandard high-density iTBS regimen: 720 pulses per session at 100% of the individual MT, delivered in 8 trains of 90 pulses over 5 min 52 sec for 15 sessions. Clinicians should not assume equivalence with more common protocols using 600 pulses/session and ≥20 sessions, because the modified schedule may have altered neuroplastic effects.
  2. The sample was highly selected for persistent negative symptoms: participants had schizophrenia with predominant negative symptoms for at least 2 years, SANS ≥60, SAPS ≤50, and unchanged antipsychotics for ≥4 weeks. These entry criteria make the findings most applicable to clinically stable patients with longstanding symptom burden rather than broadly to all patients with schizophrenia.
  3. Retention was reasonably strong for a neuromodulation study despite daily visits, with 127 completers out of 141 randomized and 116 patients still assessed at the 6-month follow-up. This suggests that a 3-week iTBS course with serial follow-up is operationally feasible in tertiary settings, even if efficacy over sham was not demonstrated.
  4. Adverse effects were more common with active stimulation, with local adverse effects in 17/71 (23.9%) versus 4/70 (5.7%) in sham (P = .02) and fatigue/sleepiness in 6 (8.4%) versus none (P = .01). In practice, patients should be counseled that active iTBS may increase transient tolerability issues even when serious events such as seizures are not observed.
  5. One active-treatment participant discontinued at the 12th session because of worsening aggression and insomnia attributed to treatment. Although uncommon, this highlights the need to monitor behavioral activation and sleep changes during iTBS courses in schizophrenia, not just headache or scalp discomfort.
  6. At treatment completion, 8 participants in the active group and 2 in the sham group showed significant improvement, but by 6 months the counts were 18 active and 15 sham, with no significant differences at any time point. Any early signal of benefit should therefore be interpreted cautiously unless it remains clearly separated from sham over longer follow-up.
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Physicians Postgraduate Press, Inc. (PPP) makes no warranties about the accuracy or completeness of any information published in The Journal of Clinical Psychiatry or other PPP materials, and disclaims liability for any use or non-use of that information. Clinicians should not rely solely on these materials and should exercise their own professional judgment when making patient care decisions on an individualized basis.

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