What are the considerations for using intramuscular (IM) injections for maintenance therapy in conditions like schizophrenia?

Intramuscular Injections for Maintenance Therapy

For maintenance therapy in schizophrenia, long-acting injectable (LAI) antipsychotics administered intramuscularly are recommended after demonstrated non-adherence or recurrent relapses related to partial or full non-adherence, with consideration for earlier use when avoiding covert non-adherence is a treatment priority. 1

Primary Indications for IM Maintenance Therapy

Schizophrenia Management

• LAI antipsychotics should be strongly considered for patients who have demonstrated medication non-adherence linked to repeated relapses, as non-adherence is the single most powerful predictor of relapse, with relapse rates five times higher among those who discontinue medication 1
• LAIs may be initiated when avoiding covert non-adherence is a priority in the treatment plan, even before documented non-adherence has occurred 1
• The majority of patients with schizophrenia who are readmitted to hospital have exhibited some degree of non-adherence, making LAIs a critical intervention for relapse prevention 1

Crohn's Disease Management

• Parenteral methotrexate 15 mg intramuscularly once weekly is suggested for maintenance therapy in moderate-to-severe Crohn's disease after achieving remission with higher induction doses 1
• After remission is achieved with 25 mg weekly IM methotrexate for 16-24 weeks, maintenance with 15 mg IM weekly for 40 weeks maintains clinical remission in 65% of patients versus 39% with placebo 1
• Oral methotrexate at lower doses (12.5-15 mg weekly) does not appear effective for maintenance of remission in Crohn's disease, making the IM route essential 1

Critical Technical Considerations

Injection Site Selection

• The anterolateral thigh (vastus lateralis) produces higher and more rapid peak plasma levels compared with deltoid or subcutaneous arm injections, which is particularly important for medications requiring rapid absorption 1, 2, 3
• Truncal sites (abdomen and buttocks) have thicker subcutaneous fat layers than limbs, reducing risk of inadvertent intramuscular injection when subcutaneous administration is intended 1
• For insulin injections specifically, intramuscular deposition leads to unpredictable (largely faster) absorption and blood glucose destabilization, making proper technique critical 1

Needle Length and Technique

• Risk of unintended intramuscular injection increases with longer needles, in slimmer and younger patients, males, and when using limb sites rather than truncal sites 1
• For medications requiring intramuscular administration, use ≤23-gauge needles with constant pressure at injection site for 2 minutes, particularly in patients with thrombocytopenia (platelet count ≥30,000-50,000 cells/mm³) 1

Safety Monitoring Requirements

Adverse Effects Surveillance

• For methotrexate maintenance therapy, monitor for nausea, vomiting (occurring in 40% vs 25% placebo), elevated liver enzymes, leukopenia, pancreatitis, and allergic reactions 1
• Patients treated with methotrexate may be at increased risk of non-melanoma skin cancer (OR: 8.55; 95% CI: 2.55-31.8), requiring ongoing dermatologic surveillance 1
• For antipsychotic LAIs, monitor for extrapyramidal symptoms including dystonia, parkinsonism, and akathisia, though these occur at relatively low rates with proper dosing 4

Contraindications and Precautions

• Methotrexate is teratogenic and patients must be counselled appropriately before initiating maintenance therapy 1
• Adverse reactions at injection sites including burning, pain, thrombophlebitis, tissue necrosis, and gangrene can occur with inadvertent perivascular extravasation or intra-arterial injection 3
• Local complications occur in approximately 0.4% of all IM injection recipients, though certain drugs produce injection-site complications with higher frequency 5

Duration of Maintenance Therapy

Schizophrenia

• Following a first psychotic episode with good response to treatment, longer duration of maintenance treatment is supported by longitudinal data showing medication non-adherence as the most powerful predictor of relapse over 5 years 1
• Most patients achieving symptomatic remission within 6-12 months after first episode have the most to lose from relapse, supporting extended maintenance therapy 1

Crohn's Disease

• Maintenance therapy with IM methotrexate 15 mg weekly should continue for at least 40 weeks after achieving remission, based on controlled trial data 1
• Consider methotrexate as an option for steroid-dependent patients when alternative options (including surgery) cannot be used 1

Common Pitfalls to Avoid

• Do not use oral methotrexate for Crohn's disease maintenance, as studies of oral methotrexate at 12.5-15 mg weekly have failed to demonstrate efficacy 1
• Avoid delaying LAI antipsychotic initiation until after multiple relapses have occurred, as each relapse may worsen long-term outcomes 1
• Do not assume all IM injections have equivalent absorption kinetics—injection site significantly affects pharmacokinetics, with thigh injections producing more rapid and higher peak levels than arm injections 1, 2, 3
• Ensure proper needle length selection to avoid inadvertent intramuscular injection when subcutaneous administration is intended, or inadequate depth when intramuscular administration is required 1