Protocol submitted to IRB:

TRANSCRANIAL MAGNETIC STIMULATION (TMS) OF LEFT DORSOLATERAL PREFRONTAL CORTEX AND LEFT TEMPOROPARIETAL CORTEX ADJUVANT THERAPY IN SCHIZOPHRENIFORM DISORDER AND SCHIZOPHRENIA PARTIAL RESPONDERS WITH 2 MONTHS FOLLOW UP

Principal investigator: Stefano Pallanti, MD PhD

Schizophreniform disorder is a serious mental disorder with symptoms similar to those of schizophrenia. Early diagnosis of this disorder is crucial, as is early intervention with medication, supportive therapy, and patient and family education. Schizophreniform disorder is characterized by the presence of the symptoms of schizophrenia, but it is distinguished from that condition by its shorter duration, which is at least 1 month but less than 6 months. Unlike schizophrenia, in which prodromal symptoms may develop over several years, schizophreniform disorder requires, among other features, a rather rapid period from the onset of prodromal symptoms to the point at which all criteria for schizophrenia (except duration and deterioration) are met (≤ 6 months). The persistence of symptoms beyond 6 months predicts a worse prognosis for schizophrenia as compared with schizophreniform disorder: untreated psychosis is associated with higher scores for overall psychopathology, positive and negative symptoms and with a lower level of functioning. According to the American Psychiatric Association, approximately two thirds of patients diagnosed with schizophreniform disorder progress to a diagnosis of schizophrenia.

At present, treatments for this disorder include general treatment approaches (i.e. psychoterapy, family and social-education therapies and pharmacotherapy): pharmacotherapy is similar to that for schizophrenia (i.e. risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole). The general aims of treatment are protecting and stabilizing the patient, minimizing the social consequences and resolving target symptoms with minimal adverse effects.

The most common definition of treatment-resistant schizophrenia (TRS) denotes patients with schizophrenia who, despite at least two adequate trials of classical neuroleptic drugs, have persistent moderate to severe positive, or disorganisation, or negative symptoms together with poor social and work function over a prolonged period of time. This definition reflects the viewpoint of people with this illness, their family members, and mental health care givers. Approximately 30% (range 10-45%) of schizophrenic patients meet these criteria. Patients with treatment-resistant schizophrenia may manifest one or more of the classical subtypes of schizophrenia which may differ biologically in terms of neurochemistry and structural brain abnormalities, e.g. ventricular enlargement. They usually have poorer premorbid function, an earlier age at onset of positive symptoms, are more likely to be male than female, and may have various quantitative types of cortical or ventricular abnormalities evident with computer tomography or magnetic resonance imaging scans. There are no established qualitative differences in cognitive dysfunction between the two groups of patients with schizophrenia, but cognitive impairment is more severe in treatment-resistant patients. Treatment-resistant schizophrenia does not usually respond to increased dosages of neuroleptic drugs, switching to other types of neuroleptics, or adding adjunctive agents such as benzodiazepines, antidepressants, anticonvulsants or lithium carbonate. This pilot study will assess the feasibility of a non-invasive technique of neuromodulation, Transcranial Magnetic Stimulation (TMS), as an add-on to antipsychotics and directed to ameliorate cognitive functions and to reduce auditory hallucinations, typical in schizophreniform disorder. For this pilot study, a rTMS treatment with double target stimulation will be used to enhance cognitive functions and reduce deficits in this domain and to reduce auditory hallucinations. The stimulation will be administered over specific brain areas thought to be involved in cognitive functions (the dorsolateral prefrontal cortex - DLPFC) and in auditory hallucinations (temporoparietal cortex - TPC: T3P3).