Long-Term Bonding Efficacy of CAD/CAM Hybrid Restorative Materials and Universal Adhesives.

OBJECTIVES: In-office and lab milled prostheses are the staple for indirect restorations. It is therefore critical to determine their long-term bonding durability. METHODS: CAD/ CAM blocks of two classes of restorative materials: 1) a nano-ceramic reinforced polymer matrix (NCPM) and, 2) a polymer-infiltrated ceramic network (PICN) were bonded using four different universal adhesives (UA) and silane systems. A lithium disilicate glassceramic (LDS) was used as a reference. The blocks were bisected and bonded with different UA/resin-cement pairs. Bonded blocks were then cut into 1.0x1.0x12.0 mm bar specimens for microtensile bond testing. Half the bars were subjected to bond strength testing immediately and the other half after aging by 50,000 thermal cycles between 5°C and 55°C. ANOVA and post-hoc tests were used to compare mean bond strength among groups. RESULTS: NCPM presented consistently high bond strength regardless of bonding techniques, while the bond strength of PICN and LDS were lower when bonded with UA relative to traditional silanes. The more hydrophilic UA produced higher bond strengths. DISCUSSION: Glass-ceramics exhibited lower bond strength with UA than the conventional etch-rinse-silane techniques. However, UAs preserved bonding interface in the long-term. SIGNIFICANCE: NCPM displayed superior bond strength relative to PICN and LDS regardless of the type of adhesives and bonding techniques.

The Histopathology of Oral Cancer Pain in a Mouse Model and a Human Cohort.

Oral cancer patients often have severe, chronic, and mechanically induced pain at the site of the primary cancer. Oral cancer pain is initiated and maintained in the cancer microenvironment and attributed to release of mediators that sensitize primary sensory nerves. This study was designed to investigate the histopathology associated with painful oral cancers in a preclinical model. The relationship of pain scores with pathologic variables was also investigated in a cohort of 72 oral cancer patients. Wild-type mice were exposed to the carcinogen, 4-nitroquinoline 1-oxide (4NQO). Nociceptive (pain) behavior was measured with the dolognawmeter, an operant device and assay for measuring functional and mechanical allodynia. Lesions developed on the tongues and esophagi of the 4NQO-treated animals and included hyperkeratoses, papillomas, dysplasias, and cancers. Papillomas included lesions with benign and dysplastic pathological features. Two histologic subtypes of squamous cell carcinomas (SCCs) were identified-SCCs with exophytic and invasive components associated with papillary lesions (pSCCs) and invasive SCCs without exophytic histology (iSCCs). Only the pSCC subtype of tongue cancer was associated with nociceptive behavior. Increased tumor size was associated with greater nociceptive behavior in the mouse model and more pain experienced by oral cancer patients. In addition, depth of invasion was associated with patient-reported pain. The pSCC histology identifies 4NQO-induced tongue cancers that are expected to be enriched for expression and release of nociceptive mediators.

Nuclear F-actin Cytology in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma.

Oral cavity cancer has a low 5-y survival rate, but outcomes improve when the disease is detected early. Cytology is a less invasive method to assess oral potentially malignant disorders relative to the gold-standard scalpel biopsy and histopathology. In this report, we aimed to determine the utility of cytological signatures, including nuclear F-actin cell phenotypes, for classifying the entire spectrum of oral epithelial dysplasia and oral squamous cell carcinoma. We enrolled subjects with oral potentially malignant disorders, subjects with previously diagnosed malignant lesions, and healthy volunteers without lesions and obtained brush cytology specimens and matched scalpel biopsies from 486 subjects. Histopathological assessment of the scalpel biopsy specimens classified lesions into 6 categories. Brush cytology specimens were analyzed by machine learning classifiers trained to identify relevant cytological features. Multimodal diagnostic models were developed using cytology results, lesion characteristics, and risk factors. Squamous cells with nuclear F-actin staining were associated with early disease (i.e., lower proportions in benign lesions than in more severe lesions), whereas small round parabasal-like cells and leukocytes were associated with late disease (i.e., higher proportions in severe dysplasia and carcinoma than in less severe lesions). Lesions with the impression of oral lichen planus were unlikely to be either dysplastic or malignant. Cytological features substantially improved upon lesion appearance and risk factors in predicting squamous cell carcinoma. Diagnostic models accurately discriminated early and late disease with AUCs (95% CI) of 0.82 (0.77 to 0.87) and 0.93 (0.88 to 0.97), respectively. The cytological features identified here have the potential to improve screening and surveillance of the entire spectrum of oral potentially malignant disorders in multiple care settings.

Effect of Sonic Resin Composite Delivery on Void Formation Assessed by Micro-computed Tomography.

OBJECTIVES: The aim of this study was to quantify the internal void volume formation in commercially available, resin composites inserted using conventional or sonic insertion methods, and analyzed using three-dimensional (3D) micro-computed tomography (µCT). METHODS AND MATERIALS: Four resin composites were evaluated: one conventional (Herculite, Ultra, Kerr Corporation, Orange, CA, USA), one flowable bulk fill (SureFil SDR Flow, Dentsply International, York, PA, USA), and two packable bulk fill (SonicFill, Kerr Corporation, and Tetric EvoCeram Bulk Fill, Ivoclar Vivadent Inc, Schaan, Liechtenstein). Eight groups were evaluated according to each resin composite type and insertion method (conventional or sonic; n=5). Forty ABS 3D-printed cylindrical molds, 5.0 mm in diameter and 4.0 mm in depth, were fabricated. For the conventional resin composite, the mold was filled incrementally (two layers), while for bulk-fill resin composites, insertion was performed in a single increment. The sonic insertion method was performed using a specific handpiece (SonicFill Handpiece, Kerr Corporation). Resin composites were light cured using a multipeak light-emitting diode light-curing unit (VALO, Ultradent Products Inc, South Jordan, UT, USA) in its regular mode. Samples were evaluated by µCT, and data were imported into software (Amira, version 5.5.2, VSG, Burlington, MA, USA) for 3D reconstruction, from which the percentage of void volume was calculated. Data were analyzed using two-way analysis of variance and Tukey post hoc test at a preset alpha of 0.05. RESULTS: The conventional insertion method resulted in reduced porosity, compared with sonic insertion, for SureFil SDR Flow and Tetric EvoCeram bulk fill. The sonic insertion method did not demonstrate any influence on void formation for Herculite Ultra or SonicFill. CONCLUSION: Results suggest that the sonic insertion method might increase void formation during resin composite delivery, depending on restorative material brand.

Gingival Fluid Inflammatory Biomarkers and Hypertension in African Americans.

Hypertension and periodontitis are highly prevalent among African Americans. This cross-sectional study investigated the relationships among inflammatory biomarkers in the gingival fluid, periodontitis, and blood pressure in these individuals. Twenty-one subjects who reported a diagnosis of hypertension and a comparison group of 26 nonhypertensive participants were enrolled. All were African Americans, non-cigarette smoking, and free from other systemic illness. Blood pressure and body mass index were assessed. A comprehensive periodontal examination was performed. Gingival fluid was collected from 3 healthy sites and 3 diseased sites when available. Samples were assessed for 8-isoprostane, interleukin 1ß, monocyte chemoattractant protein 1, tumor necrosis factor-alpha (TNFα), C-reactive protein (CRP), and matrix metalloproteinase 8. Regardless of hypertension status, diseased sites were associated with increased levels of these biomarkers. CRP and TNFα levels were also significantly higher in hypertensive than nonhypertensive individuals without diseased sites. After adjusting for demographics and body mass index, periodontal attachment loss was higher among hypertensive than nonhypertensive subjects. TNFα and CRP levels and hypertension were in the same association pathway with attachment loss. Elevated blood pressure may increase the risk of periodontitis through a localized inflammatory mechanism. Knowledge Transfer Statement: The results of this study can be used by clinicians to better understand the etiology and pathogenesis of periodontitis in hypertensive individuals in general and African Americans in particular. The information could lead to better management of periodontal disease.

Depressive symptoms account for differences between self-reported versus polysomnographic assessment of sleep quality in women with myofascial TMD.

Patients with temporomandibular disorder (TMD) report poor sleep quality on the Pittsburgh Sleep Quality Index (PSQI). However, polysomnographic (PSG) studies show meagre evidence of sleep disturbance on standard physiological measures. The present aim was to analyse self-reported sleep quality in TMD as a function of myofascial pain, PSG parameters and depressive symptomatology. PSQI scores from 124 women with myofascial TMD and 46 matched controls were hierarchically regressed onto TMD presence, ratings of pain intensity and pain-related disability, in-laboratory PSG variables and depressive symptoms (Symptoms Checklist-90). Relative to controls, TMD cases had higher PSQI scores, representing poorer subjective sleep and more depressive symptoms (both P < 0·001). Higher PSQI scores were strongly predicted by more depressive symptoms (P < 0·001, R2 = 26%). Of 19 PSG variables, two had modest contributions to higher PSQI scores: longer rapid eye movement latency in TMD cases (P = 0·01, R2 = 3%) and more awakenings in all participants (P = 0·03, R2 = 2%). After accounting for these factors, TMD presence and pain ratings were not significantly related to PSQI scores. These results show that reported poor sleep quality in TMD is better explained by depressive symptoms than by PSG-assessed sleep disturbances or myofascial pain. As TMD cases lacked typical PSG features of clinical depression, the results suggest a negative cognitive bias in TMD and caution against interpreting self-report sleep measures as accurate indicators of PSG sleep disturbance. Future investigations should take account of depressive symptomatology when interpreting reports of poor sleep.

Histomorphometric results of different grafting materials and effect of healing time on bone maturation after sinus floor augmentation: a systematic review and meta-analysis.

The aim of this systematic review was to evaluate histomorphometric variables, the amount of new bone (NB), residual graft (RG) particles and soft tissue (ST), related to various grafting materials and assess the effect of graft healing time on different histomorphometric outcomes. Studies that were published before October 2015 were electronically and manually searched in three databases. We included human studies that reported the amount of NB, RG and ST in the biopsies taken from the grafted sinuses. Based on the applied grafting materials, extracted data were categorized into different groups. Furthermore, extracted data were classified into three groups based on healing time: (i) ≤ 4.5 mo; (ii) 4.5-9 mo; and (iii) ≥ 9-13.5 mo. The search provided 791 titles. Full text analysis was performed for 258 articles resulting in 136 studies that met the inclusion criteria. Autogenous bone (AB) resulted in the highest amount of NB and lowest amount of RG compared to other grafting materials. Based on this meta-analysis, a significant difference was noticed in the amount of NB formation in grafts with a healing time of > 4.5 mo when compared to the grafts with less healing time. However, when comparing biopsies taken at 4.5-9 mo of healing (average = 6.22 mo) to the ones taken at ≥ 9-13.5 mo (average = 10.36 mo), no significant difference was noticed in the amount of NB formation of various grafts except allografts that resulted in a significantly higher percentage of NB at 9.5 mo of healing. Based on histomorphometric analysis, AB results in the highest amount of NB formation in comparison to the other grafting materials. Bone substitute materials (allografts, alloplastic materials and xenografts) seem to be good alternatives to autogenous bone and can be considered as grafting materials to avoid disadvantages related to AB, including morbidity rate, limited availability and high volumetric change. Combining AB with alloplastic materials and xenografts brings no significant advantages regarding NB formation.

Validity of self-reported sleep bruxism among myofascial temporomandibular disorder patients and controls.

Sleep bruxism (SB), primarily involving rhythmic grinding of the teeth during sleep, has been advanced as a causal or maintenance factor for a variety of oro-facial problems, including temporomandibular disorders (TMD). As laboratory polysomnographic (PSG) assessment is extremely expensive and time-consuming, most research testing this belief has relied on patient self-report of SB. The current case-control study examined the accuracy of those self-reports relative to laboratory-based PSG assessment of SB in a large sample of women suffering from chronic myofascial TMD (n = 124) and a demographically matched control group without TMD (n = 46). A clinical research coordinator administered a structured questionnaire to assess self-reported SB. Participants then spent two consecutive nights in a sleep laboratory. Audiovisual and electromyographic data from the second night were scored to assess whether participants met criteria for the presence of 2 or more (2+) rhythmic masticatory muscle activity episodes accompanied by grinding sounds, moderate SB, or severe SB, using previously validated research scoring standards. Contingency tables were constructed to assess positive and negative predictive values, sensitivity and specificity, and 95% confidence intervals surrounding the point estimates. Results showed that self-report significantly predicted 2+ grinding sounds during sleep for TMD cases. However, self-reported SB failed to significantly predict the presence or absence of either moderate or severe SB as assessed by PSG, for both cases and controls. These data show that self-report of tooth grinding awareness is highly unlikely to be a valid indicator of true SB. Studies relying on self-report to assess SB must be viewed with extreme caution.

Osteopenic consequences of botulinum toxin injections in the masticatory muscles: a pilot study.

Patients with temporomandibular muscle and joint disorder (TMJD) increasingly seek and receive treatment for their pain with botulinum toxin (BoNTA; botulinum toxin A). Used intramuscularly in therapeutic doses, it produces localised paresis. Such paresis creates risk of reduced bone mineral density, or 'disuse osteopenia'. Animal studies have frequently used BoNTA as a model of paralysis to induce bone changes within short periods. Osteopenic effects can be enduring in animals but have yet to be studied in humans. This is the first study in humans to examine bone-related consequences of BoNTA injections in the masticatory muscles, comparing oral and maxillofacial radiologists' ratings of trabecular bone patterns in the condyles of patients with TMJD exposed to multiple masticatory muscle injection sessions with BoNTA to a sample of patients with TMJD unexposed to masticatory muscle injections with BoNTA. Cone-beam computed tomography (CBCT)-derived images of bilateral condyles were evaluated in seven patients with TMJD receiving 2+ recent BoNTA treatment sessions for facial pain and nine demographically matched patients with TMJD not receiving BoNTA treatment. Two oral and maxillofacial radiologists evaluated CBCT images for evidence of trabecular changes consistent with osteopenia. Both evaluators noted decreased density in all participants exposed to BoNTA and in none of the unexposed participants (P < 0.001). No other abnormalities associated with reduced loading were detected. These findings need replication in a larger sample and over a longer time period, to ensure safety of patients with TMJD receiving multiple BoNTA injections for their pain.

The impact of a modified cutting flute implant design on osseointegration.

Information concerning the effects of the implant cutting flute design on initial stability and its influence on osseointegration in vivo is limited. This study evaluated the early effects of implants with a specific cutting flute design placed in the sheep mandible. Forty-eight dental implants with two different macro-geometries (24 with a specific cutting flute design - Blossom group; 24 with a self-tapping design - DT group) were inserted into the mandibular bodies of six sheep; the maximum insertion torque was recorded. Samples were retrieved and processed for histomorphometric analysis after 3 and 6 weeks. The mean insertion torque was lower for Blossom implants (P<0.001). No differences in histomorphometric results were observed between the groups. At 3 weeks, P=0.58 for bone-to-implant contact (BIC) and P=0.52 for bone area fraction occupied (BAFO); at 6 weeks, P=0.55 for BIC and P=0.45 for BAFO. While no histomorphometric differences were observed, ground sections showed different healing patterns between the implants, with better peri-implant bone organization around those with the specific cutting flute design (Blossom group). Implants with the modified cutting flute design had a significantly reduced insertion torque compared to the DT implants with a traditional cutting thread, and resulted in a different healing pattern.

Masticatory muscle sleep background electromyographic activity is elevated in myofascial temporomandibular disorder patients.

Despite theoretical speculation and strong clinical belief, recent research using laboratory polysomnographic (PSG) recording has provided new evidence that frequency of sleep bruxism (SB) masseter muscle events, including grinding or clenching of the teeth during sleep, is not increased for women with chronic myofascial temporomandibular disorder (TMD). The current case-control study compares a large sample of women suffering from chronic myofascial TMD (n = 124) with a demographically matched control group without TMD (n = 46) on sleep background electromyography (EMG) during a laboratory PSG study. Background EMG activity was measured as EMG root mean square (RMS) from the right masseter muscle after lights out. Sleep background EMG activity was defined as EMG RMS remaining after activity attributable to SB, other orofacial activity, other oromotor activity and movement artefacts were removed. Results indicated that median background EMG during these non-SB event periods was significantly higher (P < 0·01) for women with myofascial TMD (median = 3·31 µV and mean = 4·98 µV) than for control women (median = 2·83 µV and mean = 3·88 µV) with median activity in 72% of cases exceeding control activity. Moreover, for TMD cases, background EMG was positively associated and SB event-related EMG was negatively associated with pain intensity ratings (0-10 numerical scale) on post-sleep waking. These data provide the foundation for a new focus on small, but persistent, elevations in sleep EMG activity over the course of the night as a mechanism of pain induction or maintenance.

Nano hydroxyapatite-coated implants improve bone nanomechanical properties.

Nanostructure modification of dental implants has long been sought as a means to improve osseointegration through enhanced biomimicry of host structures. Several methods have been proposed and demonstrated for creating nanotopographic features; here we describe a nanoscale hydroxyapatite (HA)-coated implant surface and hypothesize that it will hasten osseointegration and improve its quality relative to that of non-coated implants. Twenty threaded titanium alloy implants, half prepared with a stable HA nanoparticle surface and half grit-blasted, acid-etched, and heat-treated (HT), were inserted into rabbit femurs. Pre-operatively, the implants were morphologically and topographically characterized. After 3 weeks of healing, the samples were retrieved for histomorphometry. The nanomechanical properties of the surrounding bone were evaluated by nanoindentation. While both implants revealed similar bone-to-implant contact, the nanoindentation demonstrated that the tissue quality was significantly enhanced around the HA-coated implants, validating the postulated hypothesis.

Sliding contact fatigue of graded zirconia with external esthetic glass.

Veneer chipping and fracture are common failure modes for porcelain-veneered zirconia dental restorations. We hypothesized that the graded glass/zirconia/glass with external esthetic glass (e-GZG) can increase the lifetime and improve resistance to veneer chipping and fracture relative to porcelain-veneered zirconia, while providing necessary esthetics. Previously, we have demonstrated that a graded glass-zirconia surface possesses excellent resistance to occlusal-like sliding contact fatigue. Here, we investigated the sliding contact fatigue response of this graded glass-zirconia surface with external esthetic glass. This external glass is essential for shade options, for preventing excessive wear of opposing dentition, and for protecting Y-TZP from hydrothermal degradation. e-GZG plates were bonded to composite blocks and subjected to prolonged sliding contact up to 10 million cycles at 200 N in water. The resistance to sliding contact fatigue of e-GZG matches that of monolithic Y-TZP, and both of these materials demonstrated lifetimes that were orders of magnitude longer than that of porcelain-veneered zirconia. Graded e-GZG is a promising restorative material.

Improving fatigue damage resistance of alumina through surface grading.

Porcelain-veneered alumina crown restorations often fail from bulk fracture resulting from radial cracks that initiate at the cementation surface with repeated flexure of the stiffer crown layers on the soft dentin support. We hypothesized that bulk fracture may be substantially mitigated by grading the elastic modulus at the crown surfaces. In this study, we fabricated graded structures by infiltrating glass into dense alumina plates, resulting in a diminished modulus at the surface layers. The plates were then bonded to polycarbonate substrates and subjected to fatigue loading in water. Tests were terminated when fracture occurred at the cementation tensile surface or at the fatigue endurance limit (1 million cycles). Infiltrated specimens showed a significant increase in fatigue fracture loads over non-infiltrated controls. Our results indicate that controlled elastic gradients at the surface could be highly beneficial in the design of fracture-resistant alumina crowns.

Damage maps of veneered zirconia under simulated mastication.

Zirconia-based restorations often fracture from chipping and/or delamination of the porcelain veneers. We hypothesized that veneer chipping/delamination is a result of the propagation of near-contact-induced partial cone cracks on the occlusal surface under mastication. Masticatory loading involves the opposing tooth sliding along the cuspal inner incline surface with an applied biting force. To test this hypothesis, we cemented flat porcelain-veneered zirconia plates onto dental composites and cyclically loaded them (contact-slide-liftoff) at an inclination angle as a simplified model of zirconia-based restorations under occlusion. In light of in situ observation of damage evolution in a transparent glass/zirconia/polycarbonate trilayer, post mortem damage evaluation of porcelain/zirconia/composite trilayers by a sectioning technique revealed that deep-penetrating occlusal surface partial cone fracture is the predominant fracture mode of porcelain veneers. Clinical relevance is discussed.

Prevalence of myofascial temporomandibular disorder in US community women.

This study estimates the prevalence of the myofascial subtype of temporomandibular disorders (M-TMD) defined by Research Diagnostic Criteria (RDC), and relates that prevalence to the surveyed report of facial pain. From among 20 000 women selected at random in the NY metropolitan area who completed a telephone survey of facial pain, 2000 were invited for an RDC/TMD examination; 782 examinations were completed. Prevalence was estimated in analyses that were weighted to correct sampling biases. Differences among demographic strata were evaluated with logistic regression. The prevalence of M-TMD was estimated to be 10.5% (95% CL = 8.5-13.0%). Prevalence was significantly higher among younger women, among women of lower socio-economic status, among Black women, and among non-Hispanic women. The report of facial pain in the telephone survey (10.1%) had high specificity for M-TMD diagnosis (94.7%), but low sensitivity (42.7%). M-TMD is a fairly common disorder among American women. Among those reporting facial pain during the last month, half met RDC palpation criteria for M-TMD; thus, a formal physical examination is imperative to establish this diagnosis. Prevalence varies with age, socio-economic status, race and Hispanic ethnicity. A substantial number of RDC-diagnosed cases of M-TMD did not report facial pain in the survey; the reason for this requires further study.

Reliability of clinician judgements of bruxism.

Bruxism is considered to be a parafunctional disorder requiring treatment and is viewed as a risk factor for the development of temporomandibular disorders (TMDs). The purpose of this investigation is to examine the reliability of clinician judgements of bruxism severity. Twenty dentists who are faculty members in a dental school examined 29 stone casts and gold-plated models of individual teeth for evidence of bruxism. Ordinal ratings of bruxism severity for the 29 augmented models were made on two occasions, approximately 3 months apart. Inter-rater reliability among all clinicians, evaluated using intraclass correlation coefficients (ICCs), was poor at both time one and time two (i.e. ICC = 0.33 and 0.32, respectively), with somewhat better reliability found among those clinicians with above-average time elapsed since completion of dental training (i.e. ICC = 0.48 and 0.50 for time 1 and time 2, respectively). Three-month test-retest reliabilities were fair (ICC = 0.46) for the full group of raters and were unrelated to clinicians' degree of confidence in their ratings. These results indicate a need to standardize methods for clinical assessment of bruxism. Additionally, they have implications for studies using clinical assessments of bruxism to test the association between bruxism and other conditions such as TMDs.

Materials design of ceramic-based layer structures for crowns.

Radial cracking has been identified as the primary mode of failure in all-ceramic crowns. This study investigates the hypothesis that critical loads for radial cracking in crown-like layers vary explicitly as the square of ceramic layer thickness. Experimental data from tests with spherical indenters on model flat laminates of selected dental ceramics bonded to clear polycarbonate bases (simulating crown/dentin structures) are presented. Damage initiation events are video-recorded in situ during applied loading, and critical loads are measured. The results demonstrate an increase in the resistance to radial cracking for zirconia relative to alumina and for alumina relative to porcelain. The study provides simple a priori predictions of failure in prospective ceramic/substrate bilayers and ranks ceramic materials for best clinical performance.

How separate are the sensory, emotional, and motivational dimensions of pain? A multidimensional scaling analysis.

UNLABELLED: To map the structure of the space generated by verbal descriptors of pain, 41 male college students made pairwise similarity judgments to all possible pairings of 16 words that describe experiences commonly associated with noxious electrical stimulation. Individual Differences Scaling (INDSCAL) yielded four dimensions (D) in the group stimulus space: D-1, Intense to Moderate Experiences, contained two attributes: Strong Sensations and Strong Emotions; D-2, Moderate to Weak Experiences, exhibited two attributes: Moderate Sensations and Moderate Emotions; D-3, Motivational State, possessed two attributes: Pain and Arousal Level; D-4, Sensory Qualities, exhibited two attributes: Pain and Somatosensory Qualities. The interpretation of the dimensions was supported by Preference Mapping (PREFMAP) and by correlations between subject weights and (a) psychological tests and (b) responses to noxious electrical stimuli. CONCLUSION: semantically, the pain attribute or component of the total pain-suffering experience pervades emotional, motivational and somatosensory attributes. Pain is not an independent dimension. This means that a score on a pain rating scale is not a pure measure of the patient's pain, but is heavily influenced in unknown ways by the patient's emotional and motivational state.

A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression.

OBJECTIVE: The atypical subtype of depression appears to be both well validated and common. Although monoamine oxidase inhibitors are effective in treating atypical depression, their side effects and prescription-associated dietary restrictions reduce their suitability as a first-line treatment. The objective of this study was to estimate the efficacy of the selective serotonin reuptake inhibitor (SSRI) fluoxetine in the treatment of major depression with atypical features. METHOD: One hundred fifty-four subjects with DSM-IV major depression who met the Columbia criteria for atypical depression were randomly assigned to receive fluoxetine, imipramine, or placebo for a 10-week clinical trial. Imipramine was included because its known efficacy for treatment of atypical depression helped to calibrate the appropriateness of the study group. RESULTS: In both intention-to-treat and completer groups, the effectiveness of both fluoxetine and imipramine was significantly better than that of placebo. The two medications did not differ from each other in effectiveness. Significantly more patients dropped out of treatment with imipramine than with fluoxetine. Before treatment, patients on average rated themselves as very impaired on psychological dimensions of general health and moderately impaired on physical dimensions, compared with population norms. The self-ratings of patients who responded to treatment essentially normalized on these measures. CONCLUSIONS: Despite earlier data that SSRIs might be the treatment of choice, fluoxetine appeared to be no better than imipramine in the treatment of atypical depression, although fluoxetine was better tolerated than imipramine.