This prospective cohort study aims to examine and compare electrocardiogram (ECG) parameters in subjects diagnosed with Methamphetamine Use Disorder (MUD) and Methamphetamine-Induced Psychotic Disorder (MP) during inpatient psychiatric treatment. ECG findings at hospital admission and during remission prior to discharge will be evaluated and compared between groups. The study also aims to determine whether methamphetamine-induced psychosis is associated with greater ECG abnormalities and increased cardiac risk compared to methamphetamine use without psychosis.

Methamphetamine is a potent central nervous system stimulant associated with addiction, neurotoxicity, and increased cardiovascular morbidity and mortality. Chronic methamphetamine exposure leads to sympathetic nervous system activation, elevated catecholamine levels, hypertension, myocardial ischemia, arrhythmias, cardiomyopathy, and increased risk of sudden cardiac death.

Cardiovascular complications in methamphetamine users may result from repeated catecholamine surges, endothelial damage, coronary vasospasm, thrombus formation, myocardial fibrosis, and electrical instability. Electrocardiogram (ECG) abnormalities such as prolonged QTc interval, QT dispersion (QTd), Tp-e interval prolongation, Tp-e/QTc ratio increase, ST depression, and P-wave dispersion may reflect arrhythmogenic risk.

Previous studies have demonstrated ECG abnormalities in subjects with Methamphetamine Use Disorder (MUD). However, electrocardiographic findings in Methamphetamine-Induced Psychotic Disorder (MP) have not been prospectively investigated. Evidence suggests that subjects with MP may have higher long-term cardiovascular risk compared to subjects with MUD.

This study is designed as a prospective cohort study conducted in the closed inpatient psychiatric ward of Elazığ Mental Health and Diseases Hospital. Subjects hospitalized with a diagnosis of MUD or MP according to DSM-5-TR criteria will be included. Only subjects with positive urine toxicology for methamphetamine at admission will be enrolled.

At hospital admission and prior to discharge (remission period), the following routine clinical data will be recorded: ECG, Complete blood count. ECG parameters to be evaluated include: QT interval, QTc interval, QRS duration, Tp-e interval, Tp-e/QTc ratio, ST depression, P-wave dispersion, QT dispersion, fragmented QRS.

ECGs will be interpreted by a cardiology specialist, and pathological findings will be documented. Psychiatric symptom severity will be assessed using the Positive and Negative Syndrome Scale (PANSS). Sociodemographic and substance use characteristics will also be recorded.

Admission ECG findings will be compared with remission ECG findings within groups, and ECG parameters will be compared between MUD and MP groups to determine whether psychosis is associated with increased cardiac risk.

Statistical analyses will be performed using SPSS version 26. Appropriate parametric or non-parametric tests will be used depending on data distribution. Independent and dependent sample analyses will be conducted. Correlation, regression, and ROC analyses will be performed where appropriate. Statistical significance will be defined as p<0.05. When the alpha value is accepted as 0.05, the beta value as 0.2 and the power as 80%, it was concluded that there should be at least 3 participants in each group. In this study, we plan to form each group with 80 participants.

1. For Methamphetamine Use Disorder (MUD) Group:

   *Inclusion Criteria:

   • Diagnosis of MUD according to DSM-5-TR
   • Medication-free for at least one month prior to admission
   • Age ≥ 18 years and <65 years
   • Provided informed consent

   For Methamphetamine Use Disorder (MUD) Group:

   *Exclusion Criteria:

   • Hypertension

   • Diabetes mellitus
   • Chronic kidney disease
   • Rheumatoid arthritis
   • Systemic lupus erythematosus
   • Cardiac illness
   • Severe neurological disorders
   • Immunological or systemic illness
   • Primary psychiatric disorders other than MUD
   • Alcohol use disorder

2. For Methamphetamine-Induced Psychotic Disorder (MP) Group:

   *Inclusion Criteria:

   • Diagnosis of MP according to DSM-5-TR
   • Medication-free for at least one month prior to admission
   • Age ≥ 18 years and <65 years
   • Provided informed consent

   For Methamphetamine-Induced Psychotic Disorder (MP) Group:

   *Exclusion Criteria:

   • Hypertension
   • Diabetes mellitus
   • Chronic kidney disease
   • Rheumatoid arthritis
   • Systemic lupus erythematosus
   • Cardiac illness
   • Severe neurological disorders
   • Immunological or systemic illness
   • Primary psychiatric disorders other than MP
   • Alcohol use disorder

3. For Healthy Control Group:

   *Inclusion Criteria:

   • No psychiatric diagnosis
   • No systemic or immunological illness
   • Medication-free for at least one month
   • Age ≥ 18 years and <65 years
   • Provided informed consent

   For Healthy Control Group:

   *Exclusion Criteria:

   • Hypertension

   • Diabetes mellitus
   • Chronic kidney disease
   • Rheumatoid arthritis
   • Systemic lupus erythematosus
   • Cardiac illness
   • Severe neurological disorders
   • Immunological or systemic illness
   • Primary psychiatric disorders other than schizophrenia
   • Alcohol/drug/substance use

The study population consisted/will be consisted of adult male inpatients aged 18-65 years who were admitted to Elazığ Mental Health and Diseases Hospital.

The methamphetamine-induced psychotic disorder (MP) group included/will include consecutive inpatients diagnosed with MP and the methamphetamine use disorder (MUD) group included/will include consecutive inpatients diagnosed with MUD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR).

Both patient groups consisted of active methamphetamine users and were hospitalized for clinical management at the time of assessment. Urine toxicology screening was performed at admission to confirm substance use status.

The Healthy Control (HC) group consisted of adult male individuals without current or past psychiatric disorders and without substance use disorders, matched to patient groups in terms of age and body mass index. HCs had no significant medical illnesses.

Deidentified individual participant data (IPD) underlying the results reported in this study [including demographic variables, electrocardiogram (ECG), complete blood count parameters, and Positive and Negative Syndrome Scale (PANSS) and Insight Assessment Scale (IAS)] will be made available to qualified researchers upon reasonable request for academic purposes.

Data will be shared after removal of all direct identifiers and in accordance with applicable ethical approvals and data protection regulations. Access to the data will require a methodologically sound research proposal and a data use agreement. Requests should be directed to the corresponding author.

Data will be available beginning 6 months after publication and will remain available for 5 years.

Access will be granted to researchers who provide a methodologically sound proposal. Requests must be approved by the principal investigator and may require a data use agreement in accordance with institutional and ethical regulations.