J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Review

Volume 17, Number 10, October 2025, pages 537-549

Non-Suicidal Self-Injury: Pain Addiction Mechanisms, Neurophysiological Signatures, and Therapeutic Advances

↓ **Table 1.** NSSI Treatments Comparison
Treatment category	Specific interventions	Mechanism of action/core processes	Evidence strength/efficacy	Precautions/side effects
NSSI: non-suicidal self-injury; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin-norepinephrine reuptake inhibitor.
Psychotherapy	Dialectical behavior therapy (DBT)	Training in emotion regulation, distress tolerance, interpersonal effectiveness, mindfulness; stage-based model	Strong evidence; significant reduction in self-injury frequency (70% reduction in studies); sustained effects; improves emotion regulation and social adaptation; reduces dropout rates	Requires structured, multi-modal implementation; demands therapist training and team support.
	Acceptance and commitment therapy (ACT)	Enhance psychological flexibility (acceptance, cognitive defusion, present moment awareness, values, committed action)	Innovative approach: studies show reduction in self-injury ideation; improved quality of life; promotion of positive behavioral changes.	Requires active patient participation and practice.
Physical interventions	Repetitive transcranial magnetic stimulation (rTMS)	Electromagnetic induction modulates cortical excitability, neuroplasticity and neurotransmitters; normalizes abnormal neural circuits	Noninvasive, minimal side effects; rapid reduction in self-injury frequency/severity (within 2 weeks); enhanced efficacy when combined with medication.	Requires specialized equipment and operators; long-term efficacy evidence is still accumulating.
Pharmacotherapy	Opioid receptor antagonists (naltrexone, buprenorphine)	Blocks opioid receptors and affects pain-reward circuit.	Potential for specific populations (impulsive, emotional dysregulation); low doses may be effective but requires more evidence.	Naltrexone: nausea, headache, may precipitate withdrawal; buprenorphine: avoid combination with benzodiazepines (respiratory depression risk).
	Mood stabilizers (lithium)	Mechanisms not fully understood, may involve endogenous opioid system; “anti-suicidal” effect in bipolar disorder.	Preventive effect on suicidal behavior in patients with comorbid bipolar disorder.	Narrow therapeutic window, high toxicity risk; requires strict monitoring of serum levels and renal/thyroid function; limited to specific cases with comorbid bipolar disorder where other treatments failed, not first-line.
	Atypical antipsychotics (aripiprazole, ziprasidone)	Modulates dopamine-serotonin system (partial agonism/antagonism).	Moderate efficacy in reducing self-injury in patients with psychotic symptoms, agitation or borderline traits.	Metabolic abnormality risks (weight gain, glucose/lipid disturbances), require long-term monitoring.
	Antidepressants (SSRIs like fluoxetine/sertraline, SNRIs like venlafaxine)	Modulates serotonin and/or norepinephrine levels.	May reduce self-injury in patients with comorbid depressive disorders.	Black box warning for children/adolescents, may increase suicide risk; require low starting dose and close monitoring.
	Combination therapy (e.g., neurofeedback + sertraline, or sertraline + olanzapine)	Neurofeedback enhances cognitive control, medication modulates neurochemistry, and potential synergistic effects.	May improve outcomes in treatment-resistant patients, but evidence needs strengthening.	Combination therapy (especially with olanzapine) significantly increases metabolic side effect risk, requires careful risk-benefit assessment and monitoring.

↓ Table 1. NSSI Treatments Comparison

Treatment category

Specific interventions

Mechanism of action/core processes

Evidence strength/efficacy

Precautions/side effects

NSSI: non-suicidal self-injury; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin-norepinephrine reuptake inhibitor.

Psychotherapy

Dialectical behavior therapy (DBT)

Training in emotion regulation, distress tolerance, interpersonal effectiveness, mindfulness; stage-based model

Strong evidence; significant reduction in self-injury frequency (70% reduction in studies); sustained effects; improves emotion regulation and social adaptation; reduces dropout rates

Requires structured, multi-modal implementation; demands therapist training and team support.

Acceptance and commitment therapy (ACT)

Enhance psychological flexibility (acceptance, cognitive defusion, present moment awareness, values, committed action)

Innovative approach: studies show reduction in self-injury ideation; improved quality of life; promotion of positive behavioral changes.

Requires active patient participation and practice.

Physical interventions

Repetitive transcranial magnetic stimulation (rTMS)

Electromagnetic induction modulates cortical excitability, neuroplasticity and neurotransmitters; normalizes abnormal neural circuits

Noninvasive, minimal side effects; rapid reduction in self-injury frequency/severity (within 2 weeks); enhanced efficacy when combined with medication.

Requires specialized equipment and operators; long-term efficacy evidence is still accumulating.

Pharmacotherapy

Opioid receptor antagonists (naltrexone, buprenorphine)

Blocks opioid receptors and affects pain-reward circuit.

Potential for specific populations (impulsive, emotional dysregulation); low doses may be effective but requires more evidence.

Naltrexone: nausea, headache, may precipitate withdrawal; buprenorphine: avoid combination with benzodiazepines (respiratory depression risk).

Mood stabilizers (lithium)

Mechanisms not fully understood, may involve endogenous opioid system; “anti-suicidal” effect in bipolar disorder.

Preventive effect on suicidal behavior in patients with comorbid bipolar disorder.

Narrow therapeutic window, high toxicity risk; requires strict monitoring of serum levels and renal/thyroid function; limited to specific cases with comorbid bipolar disorder where other treatments failed, not first-line.

Atypical antipsychotics (aripiprazole, ziprasidone)

Modulates dopamine-serotonin system (partial agonism/antagonism).

Moderate efficacy in reducing self-injury in patients with psychotic symptoms, agitation or borderline traits.

Metabolic abnormality risks (weight gain, glucose/lipid disturbances), require long-term monitoring.

Antidepressants (SSRIs like fluoxetine/sertraline, SNRIs like venlafaxine)

Modulates serotonin and/or norepinephrine levels.

May reduce self-injury in patients with comorbid depressive disorders.

Black box warning for children/adolescents, may increase suicide risk; require low starting dose and close monitoring.

Combination therapy (e.g., neurofeedback + sertraline, or sertraline + olanzapine)

Neurofeedback enhances cognitive control, medication modulates neurochemistry, and potential synergistic effects.

May improve outcomes in treatment-resistant patients, but evidence needs strengthening.

Combination therapy (especially with olanzapine) significantly increases metabolic side effect risk, requires careful risk-benefit assessment and monitoring.