Non-concordance to medication is recognised as a common problem and a challenging aspect in the treatment of schizophrenia. Some factors contributing to poor concordance include persistent adverse effects, impaired insight, disorganisation or cognitive impairment, lack of support and lack of patient education. Concordance issues may refer to a range of patient behaviours including treatment refusal, irregular use, or partial change in medication doses. These behaviours can significantly increase the risk of adverse patient outcomes such as relapse, hospitalisation, and suicide.

A trial of a depot antipsychotic treatment may be indicated in patients where inadequate concordance is evident despite implementation of psychosocial interventions. While there is no strong evidence of superior efficacy for one antipsychotic depot over another, olanzapine depot provides an atypical alternative to the typical antipsychotic depots available such as haloperidol, flupenthixol, fluphenazine, and zuclopenthixol.

Olanzapine long-acting injection (Zyprexa Relprevv®) is an antipsychotic depot consisting of the salt of olanzapine and pamoic acid. Due to the insoluble nature of the resulting pamoate salt, the release of olanzapine can take up to four weeks. Available in 210mg, 300mg and 405mg strengths, it is administered by deep intramuscular injection in the gluteal region every two to four weeks and is designed to release olanzapine slowly from the intramuscular site.

A rare, but serious, adverse effect of olanzapine long-acting injection is post-injection syndrome, or post-injection delirium/sedation syndrome (PDSS); a phenomenon whereby a patient exhibits signs and symptoms consistent with olanzapine overdose. Pre-marketing clinical studies of 59,482 Zyprexa Relprevv® injections given to 2,054 patients found that signs and symptoms consistent with olanzapine overdose were present in 0.07% of injections and 1.85% of patients.

Signs and symptoms of post-injection syndrome may include one or more of the following:

  • Sedation (ranging from mild in severity to coma)
  • Delirium (including confusion, agitation, and cognitive impairment)
  • Extrapyramidal symptoms
  • Dysarthria
  • Ataxia
  • Aggression
  • Dizziness
  • Weakness
  • Hypertension
  • Convulsions

Initial signs and symptoms appear within one hour of injection. However, have been reported to occur up to three hours later. Accidental contact between olanzapine and the bloodstream due to blood vessel injury during injection can be a causal factor.
For this reason, Zyprexa Relprevv® product information includes the following boxed warning:

“The potential for signs and symptoms of sedation and/or delirium consistent with olanzapine overdose exists after injection of Zyprexa Relprevv. Zyprexa Relprevv should be administered by appropriately qualified health professionals in a healthcare facility with access to emergency services for management of olanzapine overdose. Health professionals who prescribe or administer Zyprexa Relprevv should be aware of this potential risk and the consequent need to monitor patients for at least two hours after each injection. The two hour period should be extended as clinically appropriate for patients who exhibit any potential signs and symptoms of a post-injection syndrome event.”

The Therapeutic Guidelines recommend that patients should be warned of potential signs and symptoms of post-injection syndrome and monitored every 30 minutes for the first three hours after each injection of olanzapine depot. It should be noted that post-injection syndrome has not been linked to other depot antipsychotic formulations. While there is no specific treatment or reversal agent available to treat post-injection syndrome, full recovery is expected within 24-72 hours in most cases. During this time, patients should receive supportive care and management of their symptoms.

References:

  1. Bushe C, Falk D, Anand E, Casillas M, Perrin E, Chhabra-Khanna R, et al. Olanzapine long-acting injection: a review of first experiences of post-injection delirium/sedation syndrome in routine clinical practice. BMC Psychiatry. 2015; 15:65.
  2. Higashi K, Medic G, Littlewood K, Diez T, Granstrom O, De Hert M. Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic review. Ther Adv Psychopharmacol. 2013; 3(4): 200-18.
  3. McDonnell D, Detke H, Bergstrom R, Kothare P, Johnson J, Stickelmeyer M, et al. Post-Injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, II: investigations of mechanism. BMC Psychiatry. 2010; 10:45.
  4. National Prescribing Service. Olanzapine depot injection (Zyprexa Relprevv) for schizophrenia. Strawberry Hills: NPS Radar; 2009.
  5. Psychotropic Expert Group. Therapeutic Guidelines: Psychotropic. Version 7. Melbourne: Therapeutic Guidelines Limited; 2013.
  6. Zyprexa Relprevv® (olanzapine) Australian approved product information. West Ryde: Eli Lilly Australia Pty Ltd.

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