Role of Selective Serotonin Reuptake Inhibitors in Prognosis Dental Implants: A Retrospective Study.

BACKGROUND: Many recent research shows that antidepressants interfere with the osseointegration of implants. The main purpose of this study was to determine the association between selective serotonin reuptake inhibitors (SSRI) and dental implant failure. MATERIALS AND
METHODOLOGY: A retrospective study consisted of 410 patients (720 dental implants). Patients' records were used to retrieve the history of SSRI use and medication. The study consists of two groups. Group I (SSRI users) consisted of 128 patients (245 dental implants) patients, whereas Group II (non-SSRI users) was formed by 282 patients (475 dental implants). The implant failure rate was evaluated and statistically examined using the Chi-square test.
RESULTS: Group I had 30 implant failures with 13 (12%) males and 14 (11.8%) females, whereas Group II had 28 implant failures with 12 (6.3%) males and 16 (5.6%) females. In Group I, 26% of the implants failed in the age group >50 years, whereas it was 10.4% in Group II. However, in the age group <50 years, it was 6% and 4.2% Groups I and II, respectively. Group I shows that out of 40 implants in diabetic patients, 12 had failure, whereas in Group II, out of 32 implants placed in diabetics, 7 had failure. In smokers, 48% of the implants failed in Group I, and 29% in group II. In non-smokers the failure was seen in 7.7% cases in Group I and 2.1% cases in Group II. The difference was statistically significant (P < 0.05).
CONCLUSION: The usage of SSRIs is associated with an increased rate of implant failure. It has a deleterious effect on bone remodeling and leads to excessive osteoporosis. Copyright:

INTRODUCTION

The success of dental implants is dependent upon its ability to integrate with the surrounding bone. This integration is influenced by several factors, such as systemic diseases, periodontal disease, smoking, bruxism, bone density, bone augmentation, and implant design affect the success rate of implants.[123] Various studies have shown that certain systemic disorders and various chronic diseases induce systemic inflammation which influences the final outcome of the dental implant. The chronic use of medicines used for the treatment of these diseases may have a harmful effect on bone metabolism.[4]

Few recent clinical researches showed that selective serotonin reuptake inhibitors (SSRI) are associated with increase dental implant failure. SSRI is the widely prescribed antidepressant drug for curing depression. Today, depression is a globally prevalent disorder that affects 12% of males and 20% of females at some point in their lives.[5] Serotonin or 5-hydroxytryptamine (5-HT) is one of the chief neurotransmitters of the brain that is responsible for the feelings of well-being and happiness. Lower levels or reduced use of serotonin can lead to depression. The primary function of SSRI is that it increases the serotonin concentration by blocking the reuptake of serotonin by the neurons present in the brain at the synaptic level which helps to make serotonin available to the synaptic receptors.[6] The bone cells (osteoblast, osteoclast, and osteocytes) contain serotonin transporter (5-HTT) and receptors (5HTR). SSRI targets this 5HTR which in turn impedes osteoblastic activity, leading to disturbance in bone remodeling balance.[78] Studies also showed that SSRI also affects osteoblastic differentiation which is directly related to blockage of 5HTT.[678910]

The main purpose of this study was to find whether SSRI usage increases the chances of failure in patients with a dental implant.

MATERIALS AND METHODOLOGY

Patients' records with osseointegrated dental implants were obtained from the clinical database of the respective departments. This was a retrospective study comprising a total of 410 patients of both the genders who were rehabilitated with a total of 720 dental implants. Informed written consent was obtained from all patients included in the study.

Inclusion criteria

Study group (Group I)

Patients on SSRI, who were otherwise healthy or had a mild systemic disease included in the study group.

Control group (Group II)

Patients with no reported history of depression or with the mild systemic disease were included in control group.

Exclusion criteria

Patients with the history of any severe systemic disease, or a medical condition such as osteoporosis, hyperthyroidism, and Vitamin D deficiency that affect bone metabolisms, and those on systemic drugs such as bisphosphonates, antiepileptic drugs, antihypertensive drugs, and proton pump inhibitors known to interfere with bone metabolism.

SSRI usage history was retrieved from the patient's records. Patients were divided into two groups. The study group consisted of 128 with 245 dental implants, where a control group consisted of 282 patients with 475 implants.

In all the patients, dental implants (Nobel Biocare) were inserted on the edentulous site under local anesthesia according to the manufacturer's recommended protocol.[8] In patients with low bone density, various bone augmentation procedures such as lateral bone grafting and sinus lifting were performed 6 months before the implant placement.

Following implant surgery, all patients were advised to rinse the mouth with 0.2% chlorhexidine four times a day for 1 week. The patient was put on antibiotic therapy, augmentin 500 mg (amoxicillin + clavulanic acid) twice daily for 5 days. Acetaminophen 500 mg trice daily was prescribed as an analgesic as per requirement. Patients were instructed to be on a soft diet for at least 1 week. Sutures were after 10 days, and oral hygiene instructions were given. Before the commencement of the final prosthesis, osseointegration was examined clinically by examining any vertical or lateral signs of mobility.

Patients were recalled periodically for follow-up and looked up for factors such as prosthesis screw fracture, fracture of implant, and screw loosening. Signs of peri-implantitis such as radiolucency around implant apex and bone loss around implant were considered and recorded.[9] For calculation of P value, the Chi-square test was used.

RESULTS

Table 1 shows that Group I had 128 patients (245 implants) and Group II had 282 patients (475 implants). The difference was significant (P < 0.05).

Table 1

Patients’ distribution

Group	Group I (SSRI)	Group II (non-SSRI)	P
Number of patients	128	282	0.01
Number of implants	245	475	0.001

SSRI: Selective serotonin reuptake inhibitors

Table 2 shows that 41 patients in Group I were above 50 years of age and 87 were below 50 years, whereas 67 and 215 patients were above and below 50 years of age, respectively, in Group II. The difference was significant (P < 0.05). Group I consisted of 52 males and 76 females, whereas 122 males and 160 females formed Group II (P < 0.05). Fourteen patients in the study group and 30 patients in the control group had the habit of smoking. Twelve patients in Group I and 17 in Group II had diabetes. The difference was significant (P < 0.05).

Table 2

Comparison of parameters in both groups

Parameters	Group 1 (n=410)	Group II	P
Age (years)
>50	41 (53 implants)	67 (143 implants)	0.01
<50	87 (192 implants)	215 (332 implants)
Gender
Male	52 (101 implants)	122 (190 implants)	0.02
Female	76 (144 implants)	160 (285 implants)
Diabetes (under control)
Yes	12 (40 implants)	17 (32 implants)	0.001
No	116 (205 implants)	265 (443 implants)
Smoking
Yes	14 (27 implants)	30 (64 implants)	0.001
No	96 (implants)	252 (411 implants)

Table 3 shows the comparison between both groups, which has a statistically significant difference (P < 0.05). The failure rate in Group I was 12% and in Group II, it was 5.8%. Thus, showing that patients on antidepressants have more chances of implant failure.

Table 3

Failure rates

Group	Group I (SSRI)	Group II (non-SSRI)	P
Number of implants failed (%)	12	5.8	<0.05

SSRI: Selective serotonin reuptake inhibitors

Table 4 shows that Group I had 30 implant failures with 13 (12%) males and 17 (11.8%) females, whereas Group II had 28 implant failures with 12 (6.3%) males and 16 (5.6%) females. In Group I, 26% of implants failed in the age group >50 years, whereas it was 10.4% in Group II; 6% and 4.2% of implant failures were in the age group <50 years in the study and control groups, respectively. In smokers, 48% of implants failed in Group I, whereas, in Group II, it was 29%. In nonsmokers, it was 7.7% and 2.1% for Group I and Group II, respectively. In Group I, out of 40 implants in diabetic patients, 12 had a failure, whereas in Group II, out of 32 implants placed in diabetics, 7 had a failure.

Table 4

The failure rate in each parameter

Parameters	Group 1 (30 failures out of 282) (%)	Group II (28 failures out of 475) (%)
Age (years)
>50	15 (26)	14 (10.4)
<50	15 (6)	14 (4.2)
Gender
Male	13 (12)	12 (6.3)
Female	17 (11.8)	16 (5.6)
Diabetes (under control)
Yes	12 (30)	7 (21)
No	18 (8.7)	21 (4.7)
Smoking
Yes	13 (48)	19 (29)
No	17 (7.7)	9 (2.1)

DISCUSSION

Diem et al.[11] and Richards et al.[12] in their studies found that SSRI use is associated with low bone mineral density (BMD), thus leafing to increased bone loss and increased clinical fracture risk.

In our study, patients on SSRI showed an implant failure rate of 12% compared to healthy individuals at 5.8% [Table 3]. When Groups I and II were compared for different parameters such as age, sex, and smoking [Table 4], it was observed that the chances of implant failure were more in Group I. The results of our study were in accordance with Wu et al.[13] that concluded that SSRI might cause reduction in bone mass by impeding the bone-remodeling processes triggered by mechanical loading.

In this study, we observed that smokers had more chances of dental implant failure than nonsmokers. This was in agreement with the previous research by Alsaadi et al.[14] It can be because smoking interferes with the healing of wound after implant surgery. According to Riebel et al.,[15] nicotine impairs the formation of new bone and reduces the absorption of calcium, thus decreasing BMD.

The results showed that patients above 50 years of age have more chances of implant failure than below 50 years of age. The result was in accordance with the study by Negri et al.[16] that concluded that increasing age can affect the implant's success. In their review, Freemont and Hoyland[17] published that bone density is highest at 25–30 years of age, and as the person's age increases, bones become weaker. Age-associated bone loss is related to an uncoupling of bone formation and bone resorption activity, thus favoring osteoclasis. Other reasons that can be attributed to age-related changes are reduced systemic or local blood flow, reduction in the number of osteogenic stem cells, and their reduced proliferation and differentiation potential.[18]

In both groups, patients having diabetes had more implant failures. Moy et al.,[19] in their study, showed that patients with controlled diabetes were also at three times more risk of developing implant failure than to nondiabetic patients. Fiorellini et al.[20] reported 85% dental implant survival rate in a controlled diabetic patient. The reason for more implant failure in diabetic patients could be due to delayed healing of wound, increased risk of microvascular disease, infection, and susceptibility to periodontal disease. Altered bone and mineral metabolism have also been reported in diabetic patients which may interfere with the osseointegration process.[21]

No significant difference was observed in failure cases between males and females [Table 4]; this was in accordance with a study by Wu et al. Anitua et al.[22] and Noda et al.[23] have reported that gender does not have any significant role with implant failure, whereas Olmedo-Gaya et al.,[24] Wagenberg and Froum,[25] and Andersson et al.[26] demonstrated that gender has a significant effect on the implant loss rate.

CONCLUSION

The usage of SSRIs is associated with an increased rate of implant failure. It has a deleterious effect on bone remodeling and leads to excessive osteoporosis. The major factors that impact the success of implants are favorable bone remodeling and repair and healing in the early stages of osseointegration.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.