Study on the feasibility of pharmacist intervention on management of antidepressant treatment in late life depression under MDT: a mixed methods study

doi:10.21203/rs.3.rs-2217567/v1

Download PDF

Research Article

Study on the feasibility of pharmacist intervention on management of antidepressant treatment in late life depression under MDT: a mixed methods study

https://doi.org/10.21203/rs.3.rs-2217567/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

OBJECTIVE: To evaluate the effect of pharmacist intervention on antidepressant treatment in late life depression under multidisciplinary team (MDT).

Method: Patients with late life depression were selected from psychological department of The Afliated Wuxi Mental Health Center of Jiangnan University from Jan. 2021 to Mar. 2022, and randomly divided into observation group and control group, with 90 cases in each group. After 3 months of follow-up, the control group was given antidepressants and routine intervention, while the observation group was treated with pharmacist intervention under MDT and the same antidepressants. The Hamilton Depression scale (HAMD), medication appropriateness index (MAI), potential inappropriate medication (PIM), adherence, quality of life and satisfaction, the incidence of adverse drug events (ADEs), number of medication regimen optimization and clinician adoption rate were observed in two groups before and after intervention.

Results: At admission, there were no statistically difference in HAMD score, total MAI scores, PIM number, adherence and quality of life between two groups (P>0.05).

After intervention, HAMD scores of both groups were significantly reduced, while MMAS-8, GQOLI-74 and GWB scores were elevated. Moreover, the differences of scores before and after interventions, both the reduction in HAMD score and the increase in MMAS-8, GQOLI-74 and GWB scores, were more significant in the observation group than in the control group. Interestingly, the total MAI score and PIM number were increased in the control group after intervention, but decreased in the observation group. With the prolongation of the treatment, the number of patients with mild to moderate depression and general to high medication adherence in two groups was increased gradually, while patients with major depression and low medication adherence were decreased gradually. Meanwhile, the observation group also showed more significant difference than the control group. Low adherence patients increased substantially at 90 days treatment in control group. There was no significant difference in the incidence of ADEs between two groups (P>0.05). The quality of life in the observation group was significantly higher than control group (P<0.05). Pharmacists put forward 164 optimization suggestions of drug regimen for the observation group, among which 109 suggestions were adopted and implemented by clinicians, with an implementation rate of 66.46%. Clinicians have a high adoption rate of pharmaceutical recommendations based on therapeutic drug monitoring (TDM), individualized genetic testing and medication methods.

Conclusion: Pharmacist intervention can improve the management of antidepressant treatment in late life depression by using HAMD, MAI, PIM and MMAS-8 as main evaluation indicators under MDT.

multidisciplinary team

pharmacist intervention

late life depression

treatment management

medication appropriateness

Depressive disorder is one of the most common causes of emotional distress in later life, and reduces the quality of life of older adults significantly[1]. Late life depression (LLD) refers to the depressive disorder that occurs in people over 60 years old[2]. Recently, the prevalence of LLD has increased rapidly. The prevalence of moderate to severe depressive disorder in people aged 65 years and older is approximately 1–4% [3]. Indeed, the prevalence of depressive disorders has been further worsened by the coronavirus disease 2019 (COVID-19) pandemic[4]. LLD is a major social-public problem that significantly increases the rate of disability, all-cause mortality, and male suicide rates[5], creating a greater social burden. Changes in social status after retirement, troubling physical diseases, and the occurrence of life stress events may all induce or aggravate LLD. When LLD comorbidity with chronic diseases, it seriously affects the quality of life in older[6]. Meta-analysis shows that treatment response rate for LLD was about 48% and remission rate was only 33.7%[7]. Further, studies show that patients with LLD often complicated with cardio-cerebrovascular system, endocrine system[8], tumors and other diseases[9]. The formulation and adjustment of treatment plans require the participation of more departments. Meanwhile, many antidepressants lack of relevant research in the older[10] and patients with LLD suffer more from potentially inappropriate medication (PIM) due to the combination of chronic diseases. Therefore, more pharmacy intervention should be explored in those patients with LLD. Moreover, they often have cognitive impairment, showing a functional decline in memory, attention, execution, and expression ability, which require nurse to provide more active care, especially in comprehensive survival and specialist care. As a result, it is particularly important to establish and improve the multidisciplinary team (MDT) with the participation of doctors, pharmacists, nurses and technicians[11, 12]. Based on this, our study explored the feasibility of pharmacists’ intervention on management of antidepressant treatment in patients with LLD under MDT, with the aim to provide new ideas for the future.

Inclusion and exclusion criteria

Inclusion criteria: (1) Conform to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ( DSM-IV ) depressive episodes I or II diagnostic criteria, (2) 24-item Hamilton Depression Scale ( HAMD ) ≥ 20, (3) Age is between 60–70 years old, (4) Gender-neutral, primary school and above, (5) Life expectancy > 3 months, (6) Clear expression, conscious, no serious brain, heart, liver, lung, kidney dysfunction, (7) Voluntary participation in this study (three months), and actively cooperate with MDT standardized treatment and management of antidepressant treatment.

Exclusion criteria: (1) Difficult or unwilling to conduct drug managers, (2) Patients with disturbance of consciousness and severe mental illness, (3) Patients with severe brain, heart, liver, lung and renal dysfunction.

Drop-out criteria: (1) the disease progressed to a great extent during the intervention (patient suicide); and (2) the investigators believe the patient is unfit to continue the study.

Data source

Patients with LLD who visited the Outpatient Department of Psychology in our hospital from January 2021 to March 2022 were selected and divided into control group or observation group according to random number table method, with 90 cases in each group. There was no significant difference in gender, age, drug type and other basic data between the two groups (P > 0.05) (Table 1).

Intervention measures

Patients in control group were treated with different antidepressants according to disease and routine intervention: outpatient file was set up and patients were informed to return on time by pharmacists. Patients in observation group were given control group treatment and intervention under MDT: (1) MDT member: team members were divided into core one and extended one according to the degree of participation in treatment and responsibilities of each member was reasonably allocated. Core members included clinical pharmacists, psychiatrists, psychologists, and specialist nurses. Expanded members included endocrinologists, cardiologists, nephrologist, respiratory physicians and anti-infection pharmacists; (2) Formulation of treatment: Clinicians and pharmacists jointly received the patients, evaluated and established medical records and medication, educated patients, signed informed consent, and provided individualized treatment plan: i. MDT member fully considered the impact of age in patients with LLD on pharmacokinetics and pharmacodynamics, developed whole-process pharmaceutical care, closely monitored ADEs; and established patient pharmacy records, including: clinical pharmacist admission records, pharmacy outpatient records, pharmacy-related test records, ADEs records, pharmaceutical care records, etc. ii. After treated with antidepressants for 14 days. When the patient's HAMD score was ≥ 20 points, if there was a problem of irregular medication, PIM, or low medication adherence, pharmacist will correct it in time; if the patient's medication was standardized or the medication adherence was high, pharmacist will make an appointment for the psychiatrist to return visit and adjust the dosage or treatment plan in time until the patient's HAMD score < 20. iii. After treated with antidepressants for more than 28 days. If the patient's HAMD score was still ≥ 20 points, MDT intervention will be performed. Pharmacists will make appointments for patients to organize consultations with the participation of relevant core members, and organize extended members to assist in consultations according to physical conditions of patients. (3) Classified pharmaceutical care was explored to patients with agitation, anxiety, somatic discomfort, psychotic symptoms, suicidal behavior, cognitive impairment and sleep disorders, and case analysis was conducted regularly with clinicians according to the different clinical characteristics of patients. (4) After starting treatment, pharmacist conduct medication education for patients in observation group, including: informed patients of potential drug side effects, pay attention to their overall response to the drug, and improved patient medication adherence. Once side effects occurred, patients can immediately report to the clinicians or pharmacist for professional help.

Accessory tools

The American Geriatrics Society (AGS) Beers Criteria (AGS Beers Criteria) for Potentially Inappropriate Medication (PIM) Use in Older Adults are widely used to reduce adverse drug events (ADEs) by reducing the contact of elderly patients with PIM, providing a more comprehensive reference for the medication of elderly patients and improving the safety of medication[13]. Here we use AGS Beers Criteria to evaluate patient’s medication, which containing following five parts: (1) PIMs use in elderly patients; (2) PIMs use in elderly patients due to drug-disease or drug-syndrome interactions that may exacerbate the disease or syndrome; (3) drugs to be used with caution in elderly patients; (4) potentially clinically important drug-drug interactions that should be avoided in elderly patients; (5) medications that should be avoided or have their dosage reduced with varying levels of kidney function in elderly patients.

Observed indexes

Main observed indexes

Curative effect and medication appropriateness index (MAI)

The HAMD scale of the two groups were observed before intervention (d₀), 7 days (d₇), 14 days (d₁₄), 28 days (d₂₈), 60 days (d₆₀) and 90 days (d₉₀) after intervention. A total score of more than 35 points indicates severe depression; the total score of more than 20 points suggests that the current mild to moderate depression; total score less than 8 points suggests no depressive symptoms. In practical research, in order to facilitate statistics, this experiment was divided into statistical intervals of < 8 points, 8–20 points, 20–30 points, 30–35 points and > 35 points.

The index consists of 10 drug prescription evaluation dimensions. Different evaluation dimensions have different weights, including: indications (0–3), effectiveness (0–3), dosage (0–2), drug usage (0–2), prescription accessibility (0–1), drug-drug interaction (DDI) (0–2), drug-disease interaction (0–2), repeated prescription (0–1), course of treatment (0–1), drug economy (0–1). MAI provides a reliable method for evaluating the suitability of drug therapy. These evaluation dimensions are critical to assess potential drug-related issues[14]. Among them, ‘appropriate medication’ is recorded as ‘0 point’, while ‘inappropriate medication’ is recorded as the corresponding weight points. The total score of MAI is the sum of the patient’s ten dimensions, and the two groups were observed before intervention (d₀), 7 days (d₇), 14 days (d₁₄), 28 days (d₂₈), 60 days (d₆₀) and 90 days (d₉₀) after intervention. The higher the score, the worse the patient’s medication suitability[15].

Secondary observed indexes

PIM numbers and medication adherence

The PIM numbers was counted before intervention (d₀), 7 days (d₇), 14 days (d₁₄), 28 days (d₂₈), 60 days (d₆₀) and 90 days (d₉₀) after intervention according to AGS Beers Criteria.

Medication adherence of two groups were observed before intervention (d₀), 7 days (d₇), 14 days (d₁₄), 28 days (d₂₈), 60 days (d₆₀) and 90 days (d₉₀) after intervention by using Morisky Medication Adherence Scale-8 (MMAS-8). The total score was 8 points, < 6 points for low adherence, 6 to 7 (not including 7 points) for moderate adherence, 7 to 8 points for high adherence[16] (Table 2).

Table 2

MMAS-8 scoring criteria
Item	Option (score)
1. Do you sometimes forget to take antidepressants?	Yes/No (No 1 point, Yes 0 point)
2. Have you ever forgotten to take antidepressants in the past 2 weeks?	Yes/No (No 1 point, Yes 0 point)
3. Do you reduce your dosage or stop taking antidepressants without telling your doctor when you feel aggravated or have other symptoms?	Yes/No (No 1 point, Yes 0 point)
4. Do you sometimes forget to take antidepressants when you are away?	Yes/No (No 1 point, Yes 0 point)
5. Did you take antidepressants yesterday?	Yes/No (No 0 point, Yes 1 point)
6. Do you sometimes stop taking antidepressants when you feel your depressive symptoms are under control?	Yes/No (No 1 point, Yes 0 point)
7. It is really inconvenient for some people to insist on taking antidepressants daily. Do you find it difficult to insist on taking antidepressants daily?	Yes/No (No 1 point, Yes 0 point)
8. How often do you forget to take antidepressants?	Never/occasionally/sometimes/often/all (1/0.75/0.5/0.25/0)

Adverse drug events (ADEs) and quality of life and satisfaction.

ADEs of the two groups were observed before intervention (d₀), 7 days (d₇), 14 days (d₁₄), 28 days (d₂₈), 60 days (d₆₀) and 90 days (d₉₀) after intervention. ADEs related to metabolism, allergy, gastrointestinal tract and cardiac function were recorded in the two groups. Each ADEs was an independent statistical interval.

With reference to the Generic Quality of Life Inventory-74 (GQOLI-74) and the General Well-Being Schedule (GWB), quality of life and satisfaction were observed before intervention (d₀), 7 days (d₇), 14 days (d₁₄), 28 days (d₂₈), 60 days (d₆₀) and 90 days (d₉₀) after intervention. Options are very dissatisfied (1 point), dissatisfied (2 points), somewhat dissatisfied (3 points), somewhat satisfied (4 points), satisfied (5 points), very satisfied (6 points) [17].

Statistical analysis

The measurement data were expressed as means ± SD., and two-tailed Student’s t test was applied to compare between two groups. Count data were expressed as number of cases or rate, and Chi-square test was used to compare between groups. The data was expressed as median and quartile [M (P25-P75)], if it does not conform to the normal distribution, and comparisons were performed using nonparametric rank sum test. P-values < 0.05 was considered significant. SPSS version 25.0 was used to analyze the data.

All groups have completed 3 months of pharmacist intervention and related evaluation under MDT.

The HAMD between two groups.

There was no significant difference in HAMD score between two groups (P > 0.05) before intervention. However, the HAMD scores of the both groups were significantly decreased after intervention. And the HAMD score of observation group was significantly lower than control group (P < 0.05 or P < 0.01) after intervention (Fig. 1a).

Before intervention, there was no significant difference in the number of patients in each HAMD scale interval between two groups (P > 0.05). After intervention, the number of patients with mild to moderate depression in two groups gradually increased with the prolongation of antidepressant treatment and pharmacist intervention, and that in the observation group was significantly higher when compared with the control group. The number of patients with major depression was gradually decreased, and the observation group was significantly less than control group (P < 0.05) (Fig. 2a).

The MAI and PIM number between two groups.

No significant difference was found in MAI score and PIM number between two groups (P > 0.05) before intervention. However, the MAI score of control group was higher than before, while the MAI score of observation group was significantly lower than before, and the MAI score of observation group was significantly lower than that of control group at the same time (P < 0.05 or P < 0.01) after intervention (Fig. 1b). At the same time, PIM number of control group was higher than before, while it was significantly lower than before in observation group, and the PIM number of observation group was significantly lower than that in control group at the same time (P < 0.05 or P < 0.01) after intervention (Fig. 1c).

Before intervention, there was no significant difference in the number of patients in each MAI and PIM number interval between two groups (P > 0.05). After intervention, the MAI score of observation group decreased gradually, while control group increased gradually with the prolongation of antidepressant treatment. After 14 days of treatment, the number of patients with MAI score of 1 to 2 in the observation group was significantly higher than that in control group (P < 0.05 or P < 0.01) (Fig. 2b). After intervention, the PIM number of observation group decreased gradually, while control group increased gradually with the prolongation of antidepressant treatment and pharmacist intervention (Fig. 2c).

The MMAS-8 and quality of life between two groups.

There was no significant difference in MMAS-8 score between two groups (P > 0.05) before intervention. However, MMAS-8 scores of two groups were significantly higher than those before intervention, and observation group was significantly higher than control group (P < 0.05 or P < 0.01) after intervention (Fig. 1d). The quality of life and satisfaction of patients with LLD in observation group were significantly higher than those in control group (P < 0.05 or P < 0.01) after intervention (Fig. 1e, Fig. 1f).

Before intervention, there was no significant difference in the number of patients in each medication adherence between two groups (P > 0.05). After intervention, the number of patients with low medication adherence in two groups decreased gradually, and observation group was significantly less than control group at the same time. Meanwhile, the number of patients with moderation medication adherence increased gradually, and observation group was significantly higher than that when compared to control group. Further, the number of patients with high medication adherence in observation group was significantly higher than before, as well as control group, at the same period (P < 0.05 or P < 0.01). Unexpectedly, at 90th day of treatment, patients with low medication adherence in the group increased significantly (Fig. 2d).

The ADEs and Pharmacists’ suggestions between two groups.

No ADEs such as 5-hydroxytryptamine syndrome and epilepsy occurred. There was no significant difference in the incidence of ADEs such as allergy, weight gain, elevated blood glucose, nausea and diarrhea between two groups (P > 0.05) (Table 3). (The total number of ADEs is more than the number of patients in each group due to some patients have two or more ADEs).

Pharmacists put forward 164 suggestions to the patients in observation group, 109 of which were adopted by the physicians, with the adoption rate of 66.46% (Table 4).

Table 4

Distribution of pharmacists' suggestions and the implementation of clinicians' adoption
Suggestion type	Basis	Related drugs	Suggestion numbers	Number of suggestions adopted by clinicians	Adoption rate /%
Discontinuation of drugs	Duplication	Duloxetine combined with Paroxetine, Nifedipine combined with Olmesartan Medoxomil, Omeprazole Enteric-coated Capsules combined with Esomeprazole Enteric-coated Capsules, Dopamine combined with Entacapone Didopa, Aminophylline combined with Theophylline, Aspirin combined with Clopidogrel	7	7	100.00
	No indication	Caltrate D₃, Omeprazole, Aspirin, Flupentixol and Melitracen, Kaisailu, Sodium Doculate	16	4	25.00
	Drug-drug interaction	Clopidogrel combined with Omeprazole, Olanzapine combined with Fluvoxamine Maleate, Spironolactone combined with Valsartan, Warfarin combined with Aspirin	9	3	33.33
	Drug-disease interaction	Clonazepam, Cimetidine, Prazosin, Zopiclone, Venlafaxine, Fluoxetine, Aspirin, Sodium Valproate, Citalopram	14	4	28.57
	Cause ADEs	Theophylline, Olanzapine, Reserpine, Spironolactone, Warfarin, Gliclazide, Aspirin, Chlorpheniramine, Mirtazapine	21	10	47.62
	Long course of treatment or no need to continue	Duloxetine, Omeprazole	6	3	50.00
	High blood concentration results	Escitalopram Oxalate	3	3	100.00
Replacement of drugs	Cause ADEs	Clonazepam, Omeprazole, Propranolol, Olanzapine, Aspirin, Warfarin, Citalopram	8	5	62.50
	Better efficacy	Fenofibrate, Valsartan	2	1	50.00
	Recommendations of genetic tests	Duloxetine, Sertraline, Venlafaxine, Aspirin, Olanzapine	8	8	100.00
Add drugs	Better efficacy	Oxazepam, Tandospirone, Amlodipine	4	3	75.00
	Treatment of ADEs	Huganning Tablets, Compound Glycyrrhizin, Metoprolol	3	3	100.00
Increase dosage	Better efficacy	Metformin, Escitalopram Oxalate, Sodium Valproate, Lorazepam, Acarbose, Duloxetine	12	10	83.33
	Treatment of ADEs	Propranolol	2	1	50.00
	Low blood concentration	Olanzapine	5	4	80.00
Reduce dosage	Cause ADEs	Rivaroxaban, Amlodipine, Lithium Carbonate, Agomelatine, Mirtazapine, Citalopram Hydrobromide, Sodium Valproate	9	6	66.67
	High blood concentration	Escitalopram Oxalate, Sodium Valproate	3	3	100.00
	Has produced curative effect	Oxazepam	1	1	100.00
Adjust medication time	Better efficacy	Acarbose, Rivaroxaban, Metformin, Felodipine, Omeprazole Enteric-coated Capsules, Miglitol, Nifedipine, Rabeprazole Sodium Enteric-coated Capsules, Isosorbide Mononitrate	19	18	94.74
	No need to take regularly	Atorvastatin can be taken at any time of day	4	4	100.00
Adjust medication method	Better efficacy	Rabeprazole Sodium Enteric-coated Capsules, Magnesium Aluminate, Bacillus Licheniformis Capsules	8	8	100.00
Total			164	109	66.46

Treatment strategies for patients with LLD are divided into basic therapy, medication, psychotherapy, and biophysical therapy[18]. Almost all treatments are based on medication, and antidepressant is the main measure for LLD. As a result, selective serotonin reuptake inhibitors (SSRIs) are used as first-line treatment for LLD due to their good tolerability and few side effects[19].

However, elderly patients have slow gastrointestinal absorption and are prone to suffer from gastrointestinal tract reactions[20]. With the increase of age, the first-pass effect of the elder is weakened, the clearance rate of drug metabolism decreases, and the plasma concentration is more likely to accumulate. Moreover, elderly patients have more basic diseases, quite a few diseases such as diastolic hypotension have been shown to be associated with low positive mood[21]. Meanwhile, SSRIs lead to a more sensitive response to drugs such as anticholinergic in the elderly. ADEs caused by antidepressants can aggravate or mask the related symptoms, such as dry mouth dysuria, which can aggravate urinary system reactions in patients with prostatic hyperplasia[22]. Drug-related risk increases in elders such as bleeding[23], hyponatremia[24], orthostatic hypotension[25], bone density decrease[26], and falls due to long-term or even lifetime medication. At the same time, antidepressant is more likely to increase the risk of ADEs because of complicated prescription in elderly patients[27, 28]. Therefore, antidepressant treatment management in elders is particularly important.

The management of antidepressants treatment on patients with LLD is mainly undertaken by specialist medical staff, previously. However, the mental medical resources in China are relatively scarce. Moreover, compared with pharmacists, clinicians may be less professional in pharmacokinetic and pharmacodynamic changes associated with aging. Further, numerous factors which were categorized into five main categories; namely, patient factors, medication factors, physician factors, system-based factors and other factors were thought to affect medication adherence in older adults[29]. Therefore, it is more appropriate for those patients with LLD to receive pharmacist intervention under MDT. At present, relevant studies also have shown that pharmacists play an active role in the management of antidepressants treatment[30].

In our study, we found that HAMD scores of two groups after intervention were significantly lower than before, respectively. With the prolongation of treatment and pharmacist intervention, patients with mild and moderate depression gradually increased, and patients with severe depression gradually decreased. The Results showed that the symptoms of LLD patients were improved in different degrees after antidepressant treatment. HAMD scale of the observation group was significantly lower than that of the control group at the same time, suggesting better therapeutic effects than the control group. In brief, pharmacist intervention under MDT can effectively improve the effect of antidepressant treatment. Moreover, MDT intervention has greatly improved patients' confidence in the treatment and rehabilitation of physical diseases, which also helps to relieve the depressive symptoms. Equally, pharmacist intervention may increase interpersonal communication with patients, which is also conducive to the rehabilitation of depressive disorders[31]. HAMD scale of the observation group was (9.48 ± 1.17) on the 90th day of treatment, indicating that the depression control was satisfied, basically. The results are consistent with a previous study, which reported that pharmacist intervention may improve antidepressant efficacy[32]. Besides, HAMD scale did not drop into 8 or less within the 14 days in both groups, indicating that the onset of effect on antidepressant treatment should be later than 14 days.

In this study, we found that the intervention increased the MAI score in the control group, while decreased the MAI score in the observation group. Besides, the number of PIM based on AGS Beers criteria increased gradually from day 0 to day 60 in the control group, and began to decrease on day 90. MMAS-8 test showed that the score on the 90th day was significantly lower than that on the 60th day in the control group. Meanwhile, according to the GQOLI-74 and GWB scores, the improvement on the quality of life and satisfaction of patients was lower on day 90 than on day 60. Possible reason may be that at first day (day 0), clinicians need to determine the starting dose in light of the patients' tolerance, and then titrate the drug to the effective range within 1–2 weeks according to the patient's pharmacokinetic characteristics, which may be longer for elder patients. Subsequently, dose will be adjusted on basis of the patient's condition. Therefore, in the first few weeks, patients’ adherence increases gradually, as well as PIM and MAI, due to lack of pharmacist intervention. After 90 days of treatment, the treatment plan in the control group entered consolidation or even maintenance phase duo to gradual efficacy. However, in the absence of pharmacist intervention, medication adherence decreased to varying degrees, as well as the number of therapeutic drugs, thus decreasing the number of PIM at 90th day. Besides, the frequency of interpersonal interaction in the control group was less than that in the observation group, which also had a certain impact on the quality of life and satisfaction. This suggest that outpatient event can lead to an increase in the number of PIM and a decrease in suitability, and a long course of treatment will significantly reduce patients’ medication adherence and satisfaction without pharmacist intervention. By contrast, MAI score, PIM quantity, and MMAS-8 score all showed a long-term improvement trend in the observation group. The quality of life and satisfaction gradually increased because of the long-term intervention of pharmacists, including both the comprehensive review of patients medication plan and the interpersonal interaction, indicating that the pharmacist intervention plays a positive role in improving patients' medication rationality, adherence and social rehabilitation.

No significant difference was found in the incidence of ADEs between the two groups in our study. The possible reason is that outpatients do not seek doctors immediately due to minor ADEs. That is to mean, patients would not describe the symptoms until pharmacist contacted them at the observation day. Despite our pharmacists would reorganize the relevant MDT consultation and reduce the occurrence of ADEs in the subsequent observation. As a result, most ADEs occurred before pharmacist intervention, resulting in little difference in ADE incidence between the two groups. It can be found that incidence of ADEs was high in both groups, especially constipation and dry mouth. It may be related to the sensitivity of elderly patients to drug cholinergic response due to changes in pharmacokinetics and high body responsiveness to antidepressants, which have a high anticholinergic effect. Constipation occurs at a high rate and persists throughout the whole treatment in general. Therefore, most patients need to use laxatives for quite a long time. The resulting prescription cascade may also explain the increase of MAI and PIM in older patients without intervention.

In this study, 164 pharmacy recommendations were provided by pharmacists, among which 109 suggestions were adopted and implemented by clinicians, with an implementation rate of 66.46%, and the adoption rate was slightly lower than that reported in the literature[33, 34]. The possible reasons are as follows: (1) Clinical decision-making depends on experience, patients’ response to treatment and evidence-based practice, which requires solid medical skills, perennial clinical experience and profound pharmaceutical knowledge. At present, there is a shortage of pharmacists with rich clinical experience and medical skills. Therefore, it is difficult for Chinese clinicians to fully convince the pharmaceutical advice based only on evidence medicine. For example: Citalopram is often used as a first-line antidepressant for patients with epilepsy[35] in China. Pharmacists believe that for elderly patients, citalopram has a drug-induced QT interval prolongation phenomenon with a high long-term risk. It can be replaced with cardiovascular safety drugs such as sertraline, supplemented by physical exercise[36] or psychotherapy[37] as the first-line regimen. However, clinicians believe that citalopram is commonly used in patients with epilepsy comorbid depression. In clinical practice, after the application of citalopram, there is rarely a significant increase in the frequency of epileptic seizures. Further, if the patients' mood improved, the number of seizures decreased accordingly. Likewise, if seizures have been controlled, the patients' mood improved. Therefore, clinicians still tend to use citalopram before the cardiovascular response occurs. (2) Due to the excessive outpatient’ visits and concerns about the unknown reactions after the replacement regimen, clinicians are subjectively less willing to optimize the treatment plan with clear efficacy and tolerable side effects. At the same time, a considerable number of elderly patients are reluctant to discontinue or replace the current treatment drugs, even if the unreasonable therapy including no indication of prophylactic use of calcium, no indication of laxative use, and no indication of proton pump inhibitors, etc. For example, patients may continue to take doxazate sodium for a long time after constipation have subsided. Pharmacists suggest that docusate sodium can be stopped, while some patients firmly believed that their current physical state is the result of long-term use of this drug. These two ideas of clinicians and patients influence and reinforce each other, increasing the difficulty of pharmacists to optimize the program.

Clinicians usually have a high adoption rate of pharmaceutical recommendations based on therapeutic drug monitoring (TDM) and individualized drug gene test, suggesting that drug-related tests have a high recognition in clinicians' decision-making. On one hand, TDM can quantitatively monitor drug concentration in the blood and make it possible for clinicians to intervene the concentration. Clinicians can fully consider the individual differences in pharmacokinetics to achieve precision therapy. On the other hand, accumulating evidence shows that specific gene mutations, such as the MTHFR (methylenetetrahydrofolate reductase) enzyme C677T mutation, may put elderly patients at risk of depressive disorders[38]. Individualized drug gene test analyzes the polymorphisms of genes which may affect drug metabolism in patients from the perspective of molecular genetics, and clarifies the effect of genotype on efficacy. Clinicians can intuitively obtain the patients' in vivo drug concentration data and genetic information from these reports. Meanwhile, the results showed that patients and clinicians also had a high acceptance rate of the pharmacists' suggestion of adjusting medication time and method. In our study, the improving HAMD score, MAI scale and PIM number demonstrated that pharmacist intervention plays an important role in improving efficacy and avoiding ADEs, regardless of some non-acceptance case. Further, pharmacists can deeply work with clinicians to identify drug-related problems and make recommendations immediately to minimize adverse events and improve efficacy, rather than a pharmacists’ review based on guideline afterwards. Moreover, positive health education is also essential for patients. Pharmacists can actively guide patients to choose better drug regimens in order to reduce meaningless medication. To summarize, improving efficacy and reducing the risk of adverse reactions is the basic purpose of pharmacist intervention. Pharmacists can actively explore ways that are more acceptable to Chinese clinicians and patients.

Although presenting the importance of pharmacist intervention under MDT, this study had some limitations. First, the small sample size, which may lead to the bias of the results. Second, limited by the time and cost, this research only conducted the feasibility study in outpatients, which did not set up relevant studies for inpatients. On the basis of this study, larger-scale population trials can be expanded to explore the impact of different patient treatment patterns, intervention factors, and on treatment outcomes in long-term experimental states.

To sum up, this study preliminarily demonstrated that pharmacist intervention under MDT improved the management of antidepressant treatment in patients with late life depression by using HAMD, MAI, PIM and MMAS-8 as main evaluation indicators, laying the foundation for more complete controlled experiments in the future.

MDT : multidisciplinary team; HAMD: The Hamilton Depression scale; MAI: medication appropriateness index; PIM: potential inappropriate medication; ADEs: adverse drug events; TDM: therapeutic drug monitoring; LLD: Late life depression (LLD); COVID-19: the coronavirus disease 2019; DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; AGS: The American Geriatrics Society; MMAS-8: Morisky Medication Adherence Scale-8; DDI: drug-drug interaction; GQOLI-74: Generic Quality of Life Inventory-74; GWB: General Well-Being Schedule; SSRIs: selective serotonin reuptake inhibitors

Acknowledgments

Not applicable.

Author contributions

WJ conceived the study; LJ, QLH performed literature searching and summary; WJH wrote the manuscript; and LJ edited and revised the manuscript. All authors read and approved the final manuscript.

Funding

The work is supported by the HENGRUI Foundation of Jiangsu Pharmaceutical Association (No. H202139).

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Jiangsu Provincial Rongjun Hospital (JSRJH-No.2021-L002). All participants signed informed consent.

Consent for publication

Not applicable.

Availability of data and materials

The dataset generated during and analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare no confict of interest.

Taylor WD. Clinical practice. Depression in the elderly. The New England journal of medicine2014 Sep 25;371(13):1228–36.
Alexopoulos GS. Depression in the elderly. Lancet (London, England)2005 Jun 4–10;365(9475):1961–70.
Casey DA. Depression in Older Adults: A Treatable Medical Condition. Primary care2017 Sep;44(3):499–510.
Global prevalence and burden of depressive. and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet (London, England)2021 Nov 6;398(10312):1700-12.
Craig Nelson J. Management of Late-Life Depression. Handb Exp Pharmacol. 2019;250:389–413.
Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet (London, England)2007 Sep 8;370(9590):851-8.
Kuo CY, Lin CH, Lane HY. Molecular Basis of Late-Life Depression. International journal of molecular sciences2021 Jul 10;22(14).
Linnemann C, Lang UE. Pathways Connecting Late-Life Depression and Dementia. Front Pharmacol. 2020;11:279.
Moodley S, Maisto A. Late-life depression and the family physician. South African family practice: official journal of the South African Academy of Family Practice/Primary Care2022 Jun 28;64(1):e1-e4.
Ghio L, Vaggi M, Amore M, Ferrannini L, Natta W. Unmet needs and research challenges for late-life mood disorders. Aging clinical and experimental research2014 Apr;26(2):101–14.
Maust DT, Oslin DW, Thase ME. Going beyond antidepressant monotherapy for incomplete response in nonpsychotic late-life depression: a critical review. The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry2013 Oct;21(10):973–86.
Okereke OI, Lyness JM, Lotrich FE, Reynolds CF 3rd. Depression in Late-Life: a Focus on Prevention. Focus (American Psychiatric Publishing)2013 Winter;11(1):22–31.
American Geriatrics Society. 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society2019 Apr;67(4):674–94.
Samsa GP, Hanlon JT, Schmader KE, Weinberger M, Clipp EC, Uttech KM, et al. A summated score for the medication appropriateness index: development and assessment of clinimetric properties including content validity. Journal of clinical epidemiology1994 Aug;47(8):891–6.
Hanlon JT, Schmader KE. The medication appropriateness index at 20: where it started, where it has been, and where it may be going. Drugs & aging2013 Nov;30(11):893–900.
Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive validity of a medication adherence measure in an outpatient setting. Journal of clinical hypertension (Greenwich, Conn)2008 May;10(5):348–54.
McNeill JA, Sherwood GD, Starck PL, Thompson CJ. Assessing clinical outcomes: patient satisfaction with pain management. Journal of pain and symptom management1998 Jul;16(1):29–40.
Beyer JL, Johnson KG. Advances in Pharmacotherapy of Late-Life Depression. Current psychiatry reports2018 Apr 7;20(5):34.
Xinyu S, Weihong. K, Huali W. Geriatric period depression disorder diagnosis and treatment expert consensus. The Chinese Psychiatric Journal2017 Oct 5;50(05).
Amundson CJ, Knight R, Ybarra GM, Turgeon J, Bingham JM. Mitigating the Risk of Adverse Effects Related to Augmentation Therapy for Resistant Major Depressive Disorder: A Case Report. Medicina (Kaunas, Lithuania)2022 Mar 17;58(3).
Jorm AF. Association of hypotension with positive and negative affect and depressive symptoms in the elderly. The British journal of psychiatry: the journal of mental science2001 Jun;178:553–5.
Verhamme KM, Sturkenboom MC, Stricker BH, Bosch R. Drug-induced urinary retention: incidence, management and prevention. Drug Saf. 2008;31(5):373–88.
Hoirisch-Clapauch S, Nardi AE. Antidepressants: bleeding or thrombosis? Thrombosis research2019 Sep;181Suppl 1:S23-s28.
Shysh AC, Ismail Z, Sidhu D, Guo M, Nguyen LT, Naugler C. Factors Associated with Hyponatremia in Patients Newly Prescribed Citalopram: A Retrospective Observational Study. Drugs - real world outcomes2021 Dec;8(4):555–63.
Bhanu C, Nimmons D, Petersen I, Orlu M, Davis D, Hussain H, et al. Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials. PLoS medicine2021 Nov;18(11):e1003821.
Agacayak KS, Guler R, Ilyasov B. Evaluation of the effect of long-term use of antidepressants in the SSRI group on bone density with dental volumetric tomography. Drug Des Devel Ther. 2019;13:3477–84.
Brueckle MS, Thomas ET, Seide SE, Pilz M, Gonzalez-Gonzalez AI, Nguyen TS, et al. Adverse drug reactions associated with amitriptyline - protocol for a systematic multiple-indication review and meta-analysis. Systematic reviews2020 Mar 17;9(1):59.
Sonawane KB, Cheng N, Hansen RA. Serious Adverse Drug Events Reported to the FDA: Analysis of the FDA Adverse Event Reporting System 2006–2014 Database. Journal of managed care & specialty pharmacy2018 Jul;24(7):682–90.
Yap AF, Thirumoorthy T, Kwan YH. Systematic review of the barriers affecting medication adherence in older adults. Geriatrics & gerontology international2016 Oct;16(10):1093–101.
Readdean KC, Heuer AJ, Scott Parrott J. Effect of pharmacist intervention on improving antidepressant medication adherence and depression symptomology: A systematic review and meta-analysis. Research in social & administrative pharmacy: RSAP2018 Apr;14(4):321–31.
Huang AX, Delucchi K, Dunn LB, Nelson JC. A systematic review and meta-analysis of psychotherapy for late-life depression. The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry2015 Mar;23(3):261–73.
Bunchuailua W, Samprasit N, Kotirum S, Kapol N. Impact of Pharmacist Activities in Patients With Depression: A Systematic Review and Meta-analysis of Randomized Controlled Trials. The Annals of pharmacotherapy2022 May;56(5):556–64.
Tingxi W, Yunli. X, Chang. FH, Junxian X. Y. Evaluation of medication status and intervention effect of pharmacists in elderly multiple inpatients. China Dispensary. 2019;30(22):3150–54.
Balsom C, Pittman N, King R, Kelly D. Impact of a pharmacist-administered deprescribing intervention on nursing home residents: a randomized controlled trial. International journal of clinical pharmacy2020 Aug;42(4):1153–67.
Payandemehr B, Ghasemi M, Dehpour AR. Citalopram as a good candidate for treatment of depression in patients with epilepsy. Epilepsy & behavior: E&B2015 Mar;44:96 – 7.
Mura G, Carta MG. Physical activity in depressed elderly. A systematic review. Clinical practice and epidemiology in mental health: CP & EMH2013;9:125 – 35.
Wilkinson ST, Rhee TG, Joormann J, Webler R, Ortiz Lopez M, Kitay B, et al. Cognitive Behavioral Therapy to Sustain the Antidepressant Effects of Ketamine in Treatment-Resistant Depression: A Randomized Clinical Trial. Psychother Psychosom. 2021;90(5):318–27.
Blazer DG. Depression in late life: review and commentary. The journals of gerontology Series A, Biological sciences and medical sciences2003 Mar;58(3):249–65.

Tables 1 and 3 are available in the Supplementary Files section.

No competing interests reported.

Table1and3.docx

Download PDF

Version 1

posted

You are reading this latest preprint version

Study on the feasibility of pharmacist intervention on management of antidepressant treatment in late life depression under MDT: a mixed methods study

Status:

Version 1

Abstract

Figures

Introduction

Materials And Methods

Inclusion and exclusion criteria

Data source

Intervention measures

Accessory tools

Observed indexes

Main observed indexes

Curative effect and medication appropriateness index (MAI)

Secondary observed indexes

PIM numbers and medication adherence

Adverse drug events (ADEs) and quality of life and satisfaction.

Statistical analysis

Results

Discussion

Conclusion

Abbreviations

Declarations

References

tables

Additional Declarations

Supplementary Files

Status:

Version 1