Accelerated TMS for Schizophrenia!
Multiple trials demonstrate relief of both positive and negative symptoms of schizophrenia
Welcome to The Frontier Psychiatrists. This is a quick reminder that I have an event coming up! Rapid Acting Mental Health Treatment returns on May 18th in Los Angeles. Tickets are available here. Now, onto the article.
Schizophrenia is a terrible illness for many. Historically, we have understood two domains of symptoms— “positive” and “negative” symptoms. Positive symptoms are things that shouldn’t be there— but are. Symptoms that are a little…extra. This includes hallucinations (sensory experiences that arise inside one’s mind) and delusions (fixed, false beliefs). These are the “banner” symptoms of schizophrenia that most people think about when they think of the world as “crazy.” Ironically, these positive symptoms are not remotely restricted to schizophrenia as an illness. Auditory hallucinations are very common, not just in people who suffer from an impairing illness but in people who have no disease but, at some point in their lives, end up hearing voices.
One large meta-analysis of 84,711 people found:
Mean lifetime prevalence rate of AH was 9.6% (95%CI: 6.7%-13.6%). The mean lifetime prevalence was similar in children (12.7%) and adolescents (12.4%), but these two groups differed significantly from the adults (5.8%) and the elderly (4.5%).1
Yes, that’s one in ten people hearing voices at some point. The population prevalence of schizophrenia is only about 1%. The vast majority of people with hallucinations aren’t crazy, or to be more precise, mentally ill:
25% of individuals reporting hallucinatory experiences met the diagnostic criteria for a psychotic disorder; however that leaves 75% of people experiencing AVH who are considered otherwise healthy.2
Who knew that Seal was making an epidemiology argument when he sang, “We’re never going survive unless we get a little bit crazy?”
Sorry, I love this song; give me a minute with Seal:
Ok, we are back.
When we think about schizophrenia, we often imagine these flashy symptoms. Still, those are both less directly tied to problems in life—although having psychosis can be very distressing for many—than the negative symptoms. Those symptoms are subtracting something about a person, as it were. Something is missing. Maybe it’s motivation. Our science word for that is abulia:
a neurological condition characterized by a lack of will, drive, or initiative for action, speech, and thought, often resulting in apathy and reduced motivation.
Which has its own neurocircuitry3, don’t you know!
There is also a subtraction of words to say, alogia, which is also called a “paucity of speech.” There can even be an absence of thoughts in a moment, which has been described as “thought blocking.” There are more; I’ll use a list.
Apathy: Lack of motivation, interest, and drive.
Anhedonia: Inability to experience pleasure or enjoyment.
Asociality: Withdrawal from social interactions and relationships.
Avolition: Reduced ability to initiate and persist in goal-directed activities.
Poverty of speech (alogia): Reduced speech output and difficulty communicating.
Affective flattening: Reduced expression of emotions, such as sadness, happiness, and anger.
Thanks, NHS resources. These negative symptoms…suck. They can be tremendously disabling, and unfortunately, traditional antipsychotic medicines were mostly effective in quieting positive symptoms, not waking people from their anhedonia and apathy.
However, where there is neurocircuitry, TMS researchers will soon find a way to modulate it. Thanks, to name just a few colleagues, like Shan Siddiqi, Mike Fox, David Carreon, Nolan Williams, David Carreon, Deepak Sarpal, and many others.
Today’s article focuses on two new lines of evidence that suggest this brain circuit approach may be promising for schizophrenia, starting with a new paper on the treatment of negative symptoms.
Accelerated iTBS with a personalised targeting method to treat negative symptoms of schizophrenia: A randomized controlled trial
Han et al., who published their study in Brain Stimulation on March 19th, 2025, used a kind of TMS stimulation to target the part of the left front of the brain that was most functionally connected to the Ventral Tegmental Area (VTA).4
The study found the experimental intervention was very potent at relieving negative symptoms in a sample of 80 subjects:
accelerated personalised iTBS significantly reduced negative symptoms compared to sham treatment at week 4 (Cohen’s d = 0.83),