Clinicians Can Also Benefit From Using Long-Acting Formulations

Antipsychotic medication has proven to be highly effective in reducing the risk of relapse in patients with schizophrenia. A meta-analysis found that patients who continued to take antipsychotic medications had a lower risk of relapse after 7 to 12 months compared with patients who took placebo (number needed to treat to benefit: 3—indicating a very meaningful impact) (1).

At the same time, many patients with chronic illnesses find it difficult to take medication as prescribed in a consistent fashion for long periods of time (2). This can prove to be a particular challenge for those with an illness such as schizophrenia where cognitive dysfunction, lack of insight, illness-associated stigma, lack of social supports, and adverse effects can also influence adherence.

The introduction of long-acting formulations (LAFs) of antipsychotic medications (also known as long-acting injectables) provided an opportunity to facilitate medication taking, or at least to make it clearer to prescribers when medication was being missed. A large series of studies has been conducted to determine the potential advantages of LAFs in reducing the risk of relapse and hospitalization in patients with schizophrenia compared with oral antipsychotic medications.

Three types of studies have been used to evaluate LAFs: randomized, controlled trials; so-called “mirror-image” studies; and naturalistic or cohort studies (3). In randomized, controlled trials, patients who consent are randomized to receive an LAF or an oral medicine in a double-blind fashion. These patients are then followed prospectively and compared on a number of outcome measures such as psychopathology, relapse, and/or hospitalization. In mirror-image studies, patients are switched (usually) from an oral medicine to a LAF with each person serving as his or her own control. The rates of relapse and/or hospitalization for a specified period prior to the switch are then compared with an equal period after the switch. For cohort studies, large data sets are employed to compare outcomes among those “naturalistically” receiving LAFs with those receiving oral medication on specific outcome measures, with attempts to match patient groups on variables known to be associated with risk of relapse. There are pros and cons to each one of these methods, but in looking at data from all of these sources, in my opinion, the evidence favoring the use of LAFs is quite compelling.

It is not solely a matter of reducing relapse and hospitalization, but of also reducing errors in judgment that clinicians are prone to make when they are not certain about a patient’s adherence. When a clinician is uncertain about a patient’s adherence, he or she might increase the medication dose, change or add medications, or label the patient treatment resistant, when in fact nonadherence was the problem.

In my opinion, we also need to “de-stigmatize” nonadherence. Clinicians too often have a pejorative attitude toward this phenomenon, which should be normalized rather than stigmatized so that a more positive approach can be taken toward potential solutions.

In considering the use of LAFs clinicians often assume that the patient will not accept receiving them, or they give up too quickly in a discussion of their possible use (4). Many people will not initially be positive about receiving injections. In addition to communicating clearly the potential advantages of LAFs, you may recommend the patient try the injection so they can decide for themselves whether the benefits of the medication outweigh the acute pain from the injection. The pain usually diminishes over time, as the individual becomes less anxious. This is a process that can take time. And it requires patience and persistence on the part of the clinical team.

Other clinicians may view LAFs to be too invasive or controlling and believe that they represent a loss of autonomy. In my view, the goal of the medication is to control the illness, not the patient. With all of the time that can be saved by not having to continuously try to figure out whether a patient has taken the medicine appropriately or not, clinicians who prescribe LAFs would have more time to focus on psychosocial interventions to promote autonomy. The patient can always stop the treatment regardless of the formulation, but with LAFs the relapse will be postponed longer than when oral medications are stopped (5).

Another important perspective to consider when considering LAFs for your patient is that of the caregiver/family or significant other. If anyone has lived through the challenge of a loved one experiencing a psychotic episode and not agreeing to treatment, the concern about adherence becomes quite salient and can lead to considerable friction. Such challenges can be reduced enormously when LAFs are utilized.

It often appears that the biggest obstacle to the use of LAFs comes from the treatment team rather than the patient or family (4). Clinicians need to be knowledgeable about the potential benefits and risks, comfortable addressing patients’ concerns, and able communicate well in a shared decision-making context. Decisions that are in a person’s self-interest whether diet, exercise, smoking cessation, or taking effective medications do not always come easily. ■

1. Leucht S, Tardy M, Komossa K, et al. Antipsychotic Drugs Versus Placebo for Relapse Prevention in Schizophrenia: A Systematic Review and Meta-analysis. Lancet. 2012;379:2063–71.

2. Kane JM, Kishimoto T, Correll CU. Assessing the Comparative Effectiveness of Long-Acting Injectable vs. Oral Antipsychotic Medications in the Prevention of Relapse Provides a Case Study in Comparative Effectiveness Research in Psychiatry. Journal of Clinical Epidemiology. 2013. 66(8 Suppl);S37-S41.

3. Osterberg L, Blaschke T. Adherence to Medication. NEJM. 2005;353:487-497.

4. Weiden PJ, Roma RS, Velligan DI, et al. The Challenge of Offering Long-Acting Antipsychotic Therapies: A Preliminary Discourse Analysis of Psychiatrist Recommendations for Injectable Therapy to Patients With Schizophrenia. J Clin Psychiatry. 2015;76:684-90.

5. Weiden PJ, Kim E, Bermak J, et al. Does Half-Life Matter After Antipsychotic Discontinuation? A Relapse Comparison in Schizophrenia With 3 Different Formulations of Paliperidone. J Clin Psychiatry. 2017;78:e813-20.