The Ethics of Prescription of Placebos to Patients with Major Depressive Disorder

A placebo is usually defined as a pharmacologically inert preparation prescribed more for the mental relief of the patient than for its actual effect on a disorder.[1] Placebos have been shown to be effective for patient treatment in surgery,[2] cardiology,[3] psychiatry,[4] primary care.[5] In recent years, it has also been considered for the treatment of major depressive disorder (MDD)[6] as well. This is because anti-depressants used to optimize outcomes[7] in MDD have numerous adverse side effects and can be financially expensive for use while placebos have been reported to help patients with MDD without the high costs. However, the use of placebos faces ethical challenges which may limit its use. This article hopes to illustrate these challenges using the ethical model which consists of autonomy, beneficence, nonmaleficence, and justice[8] to allow clinicians to inform the decision of using placebos for the treatment of MDD in patients.

AUTONOMY

Autonomy is defined as the “personal rule of the self that is free from both controlling interferences by others and from personal limitations that prevent meaningful choice.”[9] It differs from more commonly understood political autonomy.[10] Unlike political autonomy which may be present as long as there is liberal choice without coercion, autonomy in the context of clinical medicine requires physicians to provide the conditions for independent choice.

When patients come to physicians for guidance, they lack the knowledge to understand their condition and make informed decisions. To ensure patients have more autonomy, physicians have to present all the treatment options, explain the benefits and side effects of the therapies. This allows patients to make well-informed decisions. This makes the prescription of placebos for MDD challenging because this act implies deception.[11] This is because, during the clinical use of placebos, patients are rarely informed of its use because this information might reduce a placebo's therapeutic effect.[12] This means that the prescription of placebo will also infringe on patients’ autonomy[13] when they are denied of truthful information to make the optimal treatment choice.

BENEFICENCE, NONMALEFICENCE, AND THE DOUBLE EFFECT

Beneficence refers to actions which promote the well-being of others.[14] In MDD, this would mean that a patient can go through a psychiatric evaluation to show an improvement in his clinical symptoms. Quantitatively, this can be indicated with the use of validated MDD scales like the Hamilton Rating Scale for Depression,[15,16] Montgomery-Åsberg Depression Rating Scale, the Beck Depression Inventory, and the Zung Self-rating Depression Scale.

A closely related concept of beneficence is the nonmaleficence. Nonmaleficence refers to the aim to prevent harm. This is difficult to achieve in the modern context as there are few therapies which do not have side effects. It is hence important for doctors to balance the beneficence and nonmaleficence in a process known as rule of double effect.[17,18] It is in this area that there is a greatest debate on the prescription of placebos for the treatment of major depression.

The decision to prescribe a medication for MDD should depend on the severity of the illness. If a patient has mild to moderate depression without suicidal risk and psychosis, it is possible to perform watchful waiting.[19] If a decision is made to prescribe medication, selective serotonin reuptake inhibitor (SSRI) is the first-line treatment due to its efficacy, tolerability, and general safety in overdose.[20] Placebos have also been reported in studies to be another option for medication of MDD as they have a lower adverse effect profile and can be used at a lower financial cost.[6,21]

At this juncture, before we start thinking that placebos are equivalent to SSRI in treating MDD, it should be noted that when treating MDD, there is significant difficulty in detecting suicidal risk.[22,23,24,25,26] This failure of detection might lead to the lack of treatment for patients who could have a higher risk of pursuing suicide.[27] If treatment is initiated with antidepressants, patients will experience lower suicidal ideation[28] and lower risk for suicide attempt and deaths.[29]

Another important deficit placebos have is the unpredictability of its effects.[30] This leads to “injustice” in the treatment when some patients more benefits than others. These points against placebos are especially important for major depression as it is an illness which requires a longer course of treatment.

DISCUSSION AND CONCLUSION

Major depressive disorder is a common chronic psychiatric disorder which is frequently treated with SSRIs which are financially expensive while having a poor side effect profile. This has resulted in the suggestions for the use of placebos for MDD treatment as they have few side effects while being comparatively inexpensive.

However, this is an ethically challenging proposition. This is because the use of placebos threatens to reduce the autonomy, upset the balance of beneficence and nonmaleficence (i.e., double effect) and cause patients to suffer from injustice. This is because the usage of placebos implies deception of the patient. This deception threatens to reduce the autonomy of the patient and disrupts the therapeutic relationship between physicians and patients.

Placebo use might reduce harm to the patient (i.e., nonmaleficence), but it might also result in greater suicidal risks by the patient (i.e., beneficence) as suicidal risks often cannot be detected effectively. They will hence have a higher chance of pursuing suicide as compared to when they are on SSRI treatment. In addition, placebos do not have any evidence for reproducibility and its long-term effects, making it difficult to be used for a condition like MDD.

With the lack of evidence of improved efficacy and increased risk for patients in the use of placebos in the treatment of MDD, it is currently ethically inappropriate to prescribe placebos for MDD. This can be revisited in the future when more studies on this issue are presented.