The Local Scenario on Patient Compliance

The clinical concern of non-compliance to antidepressant treatment has been reported extensively. For instance, Sansone et al (2012) suggested that the average 6-month antidepressant non-adherence rate reached 52% in the psychiatric population while that in the primary care population was 46.2%². “About 1/3 to half of my patients may not adhere to their prescribed treatments,” Dr Pang addressed. He further noted that non-compliance occurs not only in psychiatry but also in other medical disciplines, especially in diseases requiring long-term treatments, such as diabetes and hyperlipidaemia. He stated that no immediate adverse outcome would be generated for missing a single dose might contribute to the patient’s non-compliance.   

 

A recent review by Marasine and Sankhi (2021) summarised the reasons for non-compliance in patients with depression into patient-related factors, such as forgetfulness and misconceptions; medication-related factors, including side effects and pill burden; healthcare system-related factors, sociocultural factors, and logistic factors³. Dr Pang highlighted the roles of medication-related factors, “The side effects of early-generation antidepressants would adversely impact patient compliance. Also, the dosing regimen of certain medications, say three times daily, would be difficult for patients to follow.” He commented that the success of newer antidepressants was partially attributed to the improved side effect profile and once-daily dosing.

 

Major Side Effects Associated with Conventional Antidepressants

Selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are the first-line pharmacological treatments for people with MDD and anxiety disorders. However, SSRIs and SNRIs are associated with various side effects, such as loss of appetite, headaches, and increased risk of cardiovascular and cerebrovascular events⁴. Dr Pang added that gastric side effects are commonly observed in patients treated with antidepressants. He stressed that it is essential to inform the patients about this common side effect before treatment, or they would discontinue treatment. Moreover, he advised that the gastric side effects could be managed by dose adjustment or prescription with antacid medications. “In about 50% of the patients, the gastric side effects would disappear 2 to 3 weeks after treatment has started,” Dr Pang claimed. He commented that patient compliance would be improved if the side effects were well controlled.

 

In accordance with existing literature, Dr Pang stated that sexual dysfunction is common among patients on SSRIs and SNRIs⁴. “This can be observed in more than 30% of patients clinically. However, most patients would not actively inform their physicians on this issue,” he addressed. Hence, frontline physicians should communicate actively with patients and monitor the onset of potential side effects. Delayed ejaculation, anorgasmia, and decreased libido are common symptoms of sexual dysfunction reported, whereas the impacts would continue as long as the antidepressant is taken¹. Dr Pang stated that the sexual side effects could be relieved by switching therapy.

 

Perini et al (2019) reported that cognitive impairment, which included deficits in attention, executive functions, memory, and processing speed, was prevalent among patients with MDD. Notably, the disorders tended to persist even during remission of depressive symptoms⁵. Accordingly, Dr Pang noted that about 2/3 of his MDD patients would develop cognitive impairment, with forgetfulness being the most common complaint. He added that the impact of cognitive impairment was more significant in patients on long-term treatment. Importantly, Dr Pang highlighted that multimodal antidepressants would have promising effects in improving cognition in MDD patients, “Some patients claimed to have improved memory upon the treatment”.

 

Interestingly, while fatigue is one of the common side effects reported in patients on antidepressants¹, Dr Pang reflected that some patients would sleep better with the medications. “Given no severe adverse event, the patients would keep on the treatment if they feel better with it,” he stated. In order to enhance compliance, Dr Pang suggested frontline physicians to manage patients’ expectations by educating them on the expected treatment outcomes, including potential side effects and the time required for treatment benefit onset.

 

The Pharmacological Advancement in Multimodal Antidepressant

Vortioxetine is an antidepressant with a multimodal mechanism of action that works primarily via serotonin transporter inhibition, 5-hydroxytryptamine (5-TH) 1A receptor agonism and 5-HT3 receptor antagonism. These effects on the serotonergic receptors result in enhanced antidepressant effects. Some of the serotonergic receptor interactions have been reported to regulate the release of other neurotransmitters, including norepinephrine, dopamine, acetylcholine, histamine, gamma-aminobutyric acid (GABA), and glutamate⁶. Essentially, vortioxetine enhanced neurotransmitter systems in areas of the brain involved in cognitive processes, suggesting the potential to alleviate cognitive deficits and improve functional performance⁷.

 

The efficacy of vortioxetine in controlling MDD and improving cognitive performance has been demonstrated in various clinical trials. For instance, Kim et al (2022) showed that 8-week treatment with vortioxetine yielded significant improvement in depression and anxiety severity, as well as social and cognitive functioning in adult patients with MDD⁸. Dr Pang commented that, compared to SSRIs and SNRIs, multimodal antidepressant has a preferable side effect profile with fewer cognitive side effects, but monitoring on the potential gastric side effects is needed.

 

Practical Performance of Multimodal Antidepressant

To illustrate the clinical performance of vortioxetine in real-world setting, Dr Pang presented the case of his patient, a gentleman in his 30s. The patient was referred by a general practitioner to Dr Pang in late 2017. The patient had no family history of MDD nor a history of drug abuse but had depression with suicidal ideation since his teenage. He had planned to commit suicide at the age of 30. His sleep was largely normal, he had a panic attack once on a train, thus avoid any further train rides, but had no problem with taking buses.

 

With encouragement from his girlfriend, the patient consulted medical advice for his psychiatric problem before age 30. The patient had no delusion and hallucinations. The general practitioner prescribed 50mg of sertraline for the patient and referred him to Dr Pang.

 

The patient responded to the sertraline treatment and gave up his suicide plan. Nonetheless, he still felt unhappy. Given he showed no apparent gastric side effect and no abnormality in the thyroid was identified, the sertraline treatment was stepped up to 75mg and subsequently 100mg.

 

The patient was maintained on sertraline treatment for about one year. In 2019, the patient broke up with his girlfriend during social unrest. In a consultation, Dr Pang inquired about the patient’s condition and found that the patient suffered sexual side effect with delayed ejaculation. Also, the patient claimed that he felt tired with sertraline treatment.

 

“The patient was young and needed to have long-term treatment. It was important to consider his quality of life when deciding treatment, whereas the side effects of sertraline treatment would be a concern,” Dr Pang emphasised. Thus, Dr Pang switched to prescribing 10mg of vortioxetine.

 

Upon vortioxetine treatment, the patient stayed euthymic and had his sexual function improved. The sleeping quality was also improved. The vortioxetine treatment was stepped up gradually, and the potential side effects were closely monitored, particularly the gastric side effect. Dr Pang reminded that side effects would adversely affect patient compliance, especially with prolonged treatment. The vortioxetine treatment was well-tolerated, and no medication for gastric complications was required. The patient’s outcomes were satisfactory.

 

Side Effect Matters

Treatment-related side effects of antidepressants adversely impact patient compliance. Hence, Dr Pang emphasised the importance of monitoring the onset of side effects, especially at the early stage of treatment. “Patients might discontinue treatment once side effects have developed. Proper management at the initial stage would facilitate optimal compliance in the long run,” he advised. As demonstrated in former clinical trials and the case shared by Dr Pang, vortioxetine effectively controls depressive and anxiety symptoms. Given cognitive impairment is a significant side effect concern in MDD management, the preferred cognitive outcomes achieved by vortioxetine highlight the potential benefit of the therapy.

 

References

1. Khawam et al. Cleve Clin J Med 2006; 73: 351–61.  2. Sansone et al. Innov Clin Neurosci 2012; 9: 41.  3. Marasine et al. Turkish J Pharm Sci 2021; 18: 242.  4. Braund et al. Transl Psychiatry 2021 111 2021; 11: 1–8.  5. Perini et al. Neuropsychiatr Dis Treat 2019; 15: 1249.  6. Bishop et al. Therapeutic Advances in Psychopharmacology 2021; 11: 204512532110267.  7. Jacobson et al. Curr Med Res Opin 2020; 36: 117–24.  8. Kim et al. Neuropsychopharmacol Reports 2022; 42: 21–31.

This work is supported by Lundbeck. The content of this material is based on the authors’ clinical experience and knowledge, and does not necessarily represent the official views of Lundbeck.