Understanding Monotherapy in Mental Health

Imagine a physician giving a prescription for depression, epilepsy, hypertension or another chronic illness that includes only one medicine, where other doctors have already prescribed multiple medications and combined treatments. Is it best that the doctor uses just one medicine for you? A  single-treatment therapy, also known as monotherapy, refers to using a single medication or therapeutic approach to treat a condition. Sometimes, this can be easier to manage, safer to take,  and most importantly, effective if it meets the individual’s clinical needs.  

However, monotherapy isn’t the right option for everyone. At the time of deciding if an individual needs monotherapy or combination treatment, it is influenced by the condition,  severity of symptoms, previous treatment responses, potential side effects, individual preferences, and co-existing conditions of the individual (National Cancer Institute [NCI], n.d.; National Institute of Mental Health [NIMH], 2024). 

What Exactly is Monotherapy? 

Monotherapy refers to the process in which an individual is treated for a disease or condition only by using a single therapeutic approach. Pharmacological care usually specifies the use of a single medication rather than using multiple medications together [NCI, n.d.]. Using only a single prescription sounds like a simple or even too simple choice, but it is effective.

However, this doesn’t necessarily mean ‘less treatment’. A properly chosen medication may effectively target symptoms even at its lowest dose. Similarly, psychotherapy can stand alone as a single treatment for some mental health conditions, although the term ‘monotherapy’ is generally used in relation to medication therapy. Examples in mental health may include: 

• One antidepressant prescribed to treat depression. 
• One antipsychotic medication given to treat schizophrenia. 
• One mood stabiliser to treat bipolar disorder. 
• One evidence-based psychotherapy, i.e., Cognitive-Behavioral Therapy (CBT), to treat mental illness when therapy is selected as the primary intervention. 
• One medication for dealing with specific symptoms of anxiety disorder. 

This highlights that the main aim is finding the best treatment for the person and not the least medication for them. National Institute of Mental Health (NIMH) says that all psychiatric patients require mental health treatment tailored to their specific illness and choices (NIMH,  2024).

Reasons to Choose Monotherapy 

The benefits of a single treatment approach are that it’s simple to manage. Research comparing medication effectiveness shows greater simplicity equals better adherence; however, the effectiveness of this connection does vary [Pantuzza et al., 2017]. Other potential benefits may include: 

• Avoiding dangerous side effects caused by interactions between multiple medications.
• Easier to check whether the given prescription is helping to improve the symptoms or whether any side effects are developing.  
• Lowers medication burden, making it easier to take required doses. 
• Ability to identify clearly which treatment is effectively working, and which one should be changed.  

All of these are highly applicable in the field of mental health due to its long-term requirement. A  systematic review of psychiatric patients in India found that medication nonadherence was associated with factors including polypharmacy, greater illness severity, medication costs, and negative attitudes toward medication (Semahegn et al., 2023). 

Monotherapy in Mental Health 

According to NIMH, psychotherapy treatment for mild depression alone can be very useful, whereas for moderate-severe depression, medication should be used in combination [NIMH,  2024]. The National Institute for Health and Care Excellence (NICE) has also recommended that, when antidepressants are being provided, psychotherapy is being added, or other combined medicines are being prescribed, or switching to another medicine is considered, it should only be advised with the appropriate expert direction and care [NICE, 2022].  

For anxiety disorders, medication may still be offered as a solo treatment approach where appropriate, as well as evidence-based psychological remedies like Cognitive-Behavioral  Therapy (CBT) continuing to be one of the important remedies (NIMH, 2024). PTSD displays a somewhat different picture.

The VA/DoD guidelines of 2023 indicate trauma-focused therapy is a first-line therapy for PTSD, with drugs that may be suitable where therapy isn’t accessible or isn’t desired. The guideline does not find enough evidence to advise integrating PTSD drugs regularly with therapy or with medications (U.S. Division of Veterans  Affairs, 2025).

Monotherapy vs. Combination Therapy: What Determines the Choice?

There is no universal formula. Clinicians may consider some factors: 

NICE specifically recommends considering factors such as previous treatment response, likelihood of adherence, adverse effects, physical health, and individual preferences when selecting depression treatments (NICE, 2009, 2022). 

Limitations of Monotherapy 

Clearly, there are drawbacks to taking just one medication. The limitations of a single-treatment  approach may include: 

• A single medication often fails to manage all symptoms, especially in severe, complex, or multi-condition cases and sticking with it solely for simplicity can delay effective care.  
• Evaluating response takes time, as treatments like antidepressants often require several weeks to demonstrate their full effect (NIMH, 2024). 
• Certain conditions need to be treated with combination approaches; for instance, NICE  (2022) recommends pairing an antidepressant with an antipsychotic for psychotic depression.  

Finding a Balance 

However, thinking about therapy from the standpoint of ‘less treatment’ leads to the subjective opinion that ‘treating with a single medication is less of a burden’. A single approach works better for individuals whose conditions respond well to one medication and who experience minimal side effects. It would also be easier to monitor whether it’s working effectively or not.  

Combination treatment may be appropriate when one intervention cannot adequately address the person’s symptoms or when evidence supports a combined approach. Importantly, treatment should not remain unchanged simply because it began as monotherapy. When and if Symptoms continue to worsen, new concerns arise, or progress continues to remain stagnant in one’s treatment plan, one might find the cause to re-evaluate the treatment (NICE,2022).  

Conclusion  

Monotherapy is very important and a viable option in modern healthcare; sometimes, just one well-chosen treatment is enough. This approach consists of advantages like easier monitoring,  fewer drug interactions, and lower treatment burden. Yet, its usefulness strictly relies on whether that  ‘one-medication treatment’sufficiently addresses an individual’s symptoms or condition effectively or not.

Most strikingly, mental healthcare demonstrates the inability of either monotherapy or combined therapy as a universal default or choice, given the varying degrees of mental illness. Individual differences and presentation can mean that any manner of treatment is applicable in dealing with conditions like depression, PTSD, anxiety, bipolar and psychotic disorders (NICE 2022 & NIMH  2024). Ultimately, the best treatment doesn’t necessarily consist of numerous medications. It should consist of the right treatments that are effective, appropriate, tolerable, accessible and meaningful for the individuals who are receiving them.