Efficacy of antidepressants on orofacial pain: a systematic review

Abstract

Orofacial pain is a common complaint with multiple diagnoses. There is controversy about the effectiveness of antidepressants for the management of orofacial pain disorders. In order to be able to make a best evidence choice between available antidepressants for the treatment of orofacial pain, a systematic review was conducted of existing randomized controlled trials of antidepressants. Trials were identified from the Pubmed database up to March 2012, from references in retrieved reports and from references in review articles. Six articles were found and included in this review. Four studies were randomized placebo-controlled trials and two studies were randomized active-controlled trials. Two independent investigators reviewed these articles using a 15-item checklist. All six trials were of high quality according to the 15-item criteria. Nevertheless there was limited evidence to support the effectiveness of antidepressants in orofacial pain disorders, because of the heterogeneity of treatment modalities and the low number of randomized controlled trials per diagnose. More randomized controlled trials are needed to come to a firm conclusion for the use of antidepressants for orofacial pain disorders.

Complaints in the orofacial area are not rare. Orofacial pain affects the lives of millions worldwide. The diagnosis of orofacial pain is often very challenging, especially when psychosocial factors are present. Most treatment modalities require multidisciplinary approaches.

Orofacial pain can be divided into categories such as: musculoskeletal; neuropathic; vascular; neurovascular; idiopathic; pain caused by local, distant, or systemic pathology; and psychogenic. Musculoskeletal pain is common, in particular temporomandibular pain. If a neural injury and/or irritation occurs there is a change and neuropathic pain develops. This type of pain can be divided into episodic, including trigeminal neuralgia and glossopharyngeal neuralgia, or continuous, such as herpetic and postherpetic neuralgia and tramatic neuralgia.

Antidepressants have been described as successful treatment modalities. Nevertheless, to the authors’ knowledge a consensus about the use of these drugs in orofacial pain disorders has not yet been formed.

Materials and methods

The present review was designed to investigate the evidence of the use of antidepressants in orofacial pain disorders. Which treatment modalities are effective for specific orofacial pain disorders or for orofacial pain in general.

Selection of studies

The PuMed database was used for a computer assisted search up to March 2012. The search strategy used the key words: ‘orofacial pain’, ‘oral pain’, ‘facial pain’, ‘neuralgia’, ‘trigeminal neuralgia’, ‘tendomandibular dysfunction’, ‘burning mouth syndrome’, ‘odontalgia’, ‘(post) herpetic neuralgia’, ‘stomatodynia’, ‘atypical facial pain’, ‘cancer facial pain’ in combination with ‘antidepres*’ and ‘(facial) pain’. The following limits were applied: the type of article was ‘randomized controlled trial’ and ‘controlled-clinical-trial’, and the language ‘Dutch or English’. Figure 1 shows the search strategy to identify relevant studies. Additional reports were identified from the reference lists of retrieved reports and from review articles.

Fig. 1
Search strategy used to identify studies on orofacial pain and the use of antidepressants.

Two investigators reviewed all identified trials independently to determine whether a study should be included. Inclusion criteria were single or double blinded randomized controlled trials (RCTs), dealing with patients suffering from orofacial pain disorders, with pain intensity as main outcome measure and antidepressants as treatment modality. A flow-chart of the retrieved and included studies is presented in Fig. 2 .

Fig. 2
Flow chart of the studies retrieved and included in this review.

Methodological quality of the studies

Trials concerning treatment effectiveness were scored using a 15 item criteria list ( Table 1 ). Different criteria lists measuring the methodological quality of a RCT have been described. It is not clear which list is most valid. For this systematic review the most extended item list was chosen. This list includes selection and restriction of the study group, treatment allocation, study size, prognostic comparability, drop outs, interventions, extra treatments, blinding procedure, outcome measurements, follow-up period, side effects and analysis and presentation of data. A maximum score of 100 for each study can be achieved, when each criterion was weighted. Comparability of the different treatment groups is the essence of a good clinical trial. As allocation procedure and drop-out rates are key elements in (randomized) controlled trials these criteria received the highest possible scores in the check list. Two independent investigators (W.J.J.M. Martin and T. Forouzanfar) assessed the methodological quality of the trials. In case of disagreement, consensus between the two investigators had to be found. If no agreement could be reached a third investigator was consulted. The assessment resulted in a hierarchical list in which higher scores indicate studies with a higher methodological quality.

Table 1
Methodological 15-item criteria score.
Answers Scores
A. Selection and restriction
1 Description of inclusion and exclusion criteria − −/+ + 2
2 Restriction to a homogeneous study population − −/+ + 2
B. Treatment allocation
1 Randomisation − −/+ + If yes, then
2 Allocation procedure adequate − −/+ + 10
3 Blinded allocation procedure − −/+ + 5
C. Study size
1 Smallest group bigger than 25 subjects − −/+ + 4
2 Smallest group bigger than 50 subjects − −/+ + 6
3 Smallest group bigger than 75 subjects − −/+ + 8
D. Prognostic comparability
1 Type of diagnosis − −/+ + 2
2 Baseline scores for outcome measures − −/+ + 2
3 Duration of the complaint − −/+ + 1
4 Age − −/+ + 1
5 Sex − −/+ + 1
6 Previous medication − −/+ + 1
E. Drop outs
1 No drop outs OR − −/+ + 12
2 Number of drop outs given in each group − −/+ + 2
3 Reasons for withdrawal (of drop outs) given in each group − −/+ + 2
4 Drop outs not leading to bias (less than 5%) − −/+ + 8
F. Intervention
1 Type of intervention − −/+ + 1
2 Dose − −/+ + 1
3 Treatment frequency − −/+ + 1
4 Duration of treatment − −/+ + 1
5 Compliance presented − −/+ + 2
G. Intervention
1 Type of intervention − −/+ + 1
2 Dose − −/+ + 1
3 Treatment frequency − −/+ + 1
4 Duration of treatment − −/+ + 1
5 Compliance presented − −/+ + 2
H. Extra treatment
1 No co-intervention OR − −/+ + 5
2 Co-intervention comparable between groups − −/+ + 5
I. Blinding of patient
1 Attempt at blinding − −/+ + 4
2 Blinding evaluated and successful − −/+ + 2
J. Blinding of therapist
1 Attempt at blinding − −/+ + 4
2 Blinding evaluated and successful − −/+ + 2
K. Blinding of observer
1 Attempt at blinding − −/+ + 4
2 Blinding evaluated and successful − −/+ + 2
L. Outcome measures
1 Pain intensity − −/+ + 1
2 Global improvement − −/+ + 1
3 Functional status − −/+ + 1
4 Medical consumption − −/+ + 1
5 Other − −/+ + 0.5
6 Other − −/+ + 0.5
M. Timing of measurements
1 Timing comparable − −/+ + 1
2 Measurement just after the last treatment − −/+ + 1
N. Side effects
1 Description of the side effects in each group − −/+ + 5
O. Analysis and presentation of data
1 Frequencies/mean and standard deviation/median and quartiles − −/+ + 2
2 Intention to treat analysis OR − −/+ + 4
3 Adequate correction for base line differences or drop outs − −/+ + 4

+: the item is explained in the study and all points for that item are given; −/+: it is debatable if the item is explained in the study and therefore half points of the total achievable points are given; −: the item is not explained in the study and no points are given for that item.

Statistics

Only trials with pain intensity as the main outcome measure were considered as relevant. As mentioned in the study by van Tulder et al., a cut-off point of 50 was used for the methodological quality score. A trial was qualified as high quality if the methodological score was 50 points or more. If the score was less than 50 points, the study was considered to be of low quality. The level of evidence for therapeutic intervention effectiveness was categorized according to four levels of scientific evidence, based on the quality, outcome and relevance of the studies. This includes: strong evidence, moderate evidence, limited evidence and no evidence. For strong evidence, multiple relevant, high quality trials were identified; for moderate evidence, one relevant, high quality trial and one or more relevant low quality trials were identified; for limited evidence, one relevant high quality trial or multiple relevant, low quality trials were identified; and for no evidence, one relevant, low quality trial or no relevant trials or trials with contradictory outcomes were identified.

Results

9 RCTs, with a variety of diagnose including, burning mouth syndrome, bruxism, temporomandibular joint disorders, radiation induced pain, atypical facial pain and postherpetic neuralgia were found. Two of these studies investigated the treatment of postherpetic neuralgia or neuropathic pain. One study about the treatment of chronic idiopathic pain disorders was identified. The patient populations of these three studies consisted not only of patients with orofacial pain, but also of patients with other pain disorders. These three articles were excluded because of their heterogeneous study populations and the difficulty of extrapolating these studies to ‘orofacial complaints’ alone. The hierarchical list of the quality score is demonstrated in Table 2 . The randomized placebo controlled trials are listed in Table 3 and the randomized active-controlled trials in Table 4 .

Table 2
Hierarchical list of the quality score of RCTs and antidepressants.
Authors A
4
B
15
C
8
D
8
E
12
F
6
G
6
H
5
I
6
J
6
K
6
L
5
M
2
N
5
O
6
Total
100
Tammiala-Salonen et al. (1999) 4 15 0 7.5 4 6 6 5 6 6 0 4.5 2 5 6 77
Maina et al. (2002) 3 15 0 8 12 6 6 0 0 4 0 3 2 5 6 70
Forssell et al. (2004) 2 15 0 8 4 6 6 5 4 4 0 1.5 2 5 4 66.5
Raigrodski et al. (2001) 1 15 0 4 12 4 4 0 4 4 0 2.5 2 0 2 54.5
Rizzatti-Barbosa et al. (2003) 2 5 0 5 12 4 4 5 4 4 0 1.5 2 0 5 53.5
Ehrnrooth et al. (2001) 4 10 0 7 4 4 4 5 0 0 0 1.5 2 5 6 52.5
Only gold members can continue reading. Log In or Register to continue

Jan 24, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Efficacy of antidepressants on orofacial pain: a systematic review
Premium Wordpress Themes by UFO Themes