Trends in the long-term use of benzodiazepine anxiolytics and hypnotics: A national register study for 2006 to 2014.

PURPOSE: Long-term benzodiazepine (BZD) treatment continues to be a debated topic. Because individual BZDs have different clinical profiles, we assessed the nationwide trends of long-term BZD use at active substance level during years 2006 to 2014. METHODS: This study covered all reimbursed BZD purchases (n = 408 572-521 823 annually) for adults recorded in the Finnish Prescription Register. We assessed long-term use (annual cumulative purchase of ≥180 defined daily doses) in general, and at active substance level with the most commonly used BZD anxiolytics (oxazepam, diazepam, alprazolam, and clonazepam for nonepilepsy indications) and hypnotics (zopiclone, zolpidem, and temazepam) included. The persistence rates for each substance were assessed separately. RESULTS: The prevalence of long-term BZD use among Finnish adults declined significantly from 5.3% to 3.6%, during years 2006 to 2014. Despite this decline, there was a significant increase in the long-term use of clonazepam for nonepilepsy indications and zolpidem (28.0% and 17.5%, respectively). Long-term use was common in the aged population, as well as among the users of hypnotics or clonazepam. Persistent use of 9 consecutive calendar years varied between 7.5% for incident alprazolam users and 21.0% for incident clonazepam users. CONCLUSIONS: We found a declining trend in long-term BZD use, but the decline was not uniform between the substances-the long-term use of clonazepam and zolpidem even increased. Follow-up research is needed to assess whether the decline in BZD use is accompanied by an increased use of other types of anxiolytic or hypnotic drugs or other forms of treatment.

Psychiatric (Axis I) and personality (Axis II) disorders and subjective psychiatric symptoms in chronic tinnitus.

OBJECTIVE: Chronic tinnitus has been associated with several psychiatric disorders. Only few studies have investigated these disorders using validated diagnostic interviews. The aims were to diagnose psychiatric and personality disorders with structured interviews, to assess self-rated psychiatric symptoms and elucidate temporal relations between psychiatric disorders and tinnitus. DESIGN: Current and lifetime DSM-IV diagnoses of axis-I (psychiatric disorders) and axis-II (personality disorders) were assessed using structured clinical interviews (SCID-I and -II). Current subjective psychiatric symptoms were evaluated via self-rating instruments: the Symptom Check List-90 (SCL-90), the Beck Depression Inventory, and the Dissociative Experiences Scale (DES). STUDY SAMPLE: 83 patients (mean age 51.7, 59% men) with chronic, disturbing tinnitus and a median Tinnitus Handicap Inventory score of 32. RESULTS: The rates of lifetime and current major depression were 26.5% and 2.4%. The lifetime rate of obsessive-compulsive personality disorder (type C) was 8.4%. None of the patients had cluster B personality disorder or psychotic symptoms. The SCL-90 subscales did not differ from the general population, and median DES score was low, 2.4. CONCLUSIONS: Tinnitus patients are prone to episodes of major depression and often also have obsessive-compulsive personality features. Psychiatric disorders seem to be comorbid or predisposing conditions rather than consequences of tinnitus. Clinical trial reference: ClinicalTrials.gov (ID NCT 01929837).

Electric field-navigated transcranial magnetic stimulation for chronic tinnitus: a randomized, placebo-controlled study.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) may alleviate tinnitus. We evaluated effects of electric field (E-field) navigated rTMS targeted according to tinnitus pitch. No controlled studies have investigated anatomically accurate E-field-rTMS for tinnitus. DESIGN: Effects of E-field-rTMS were evaluated in a prospective randomised placebo-controlled 6-month follow-up study on parallel groups. Patients received 10 sessions of 1 Hz rTMS or placebo targeted to the left auditory cortex corresponding to tonotopic representation of tinnitus pitch. Effects were evaluated immediately after treatment and at 1, 3 and 6 months. Primary outcome measures were visual analogue scores (VAS 0-100) for tinnitus intensity, annoyance and distress, and the Tinnitus Handicap Inventory (THI). STUDY SAMPLE: Thirty-nine patients (mean age 50.3 years). RESULTS: The mean tinnitus intensity (F3 = 15.7, p < 0.0001), annoyance (F3 = 8.8, p = 0.0002), distress (F3 = 9.1, p = 0.0002) and THI scores (F4 = 13.8, p < 0.0001) decreased in both groups over time with non-significant differences between the groups. After active rTMS, 42% and 37% of the patients showed excellent response at 1 and 3 months against 15% and 10% in the placebo group (p = 0.082 and p = 0.065). CONCLUSIONS: Despite the significant effects of rTMS on tinnitus, differences between active and placebo groups remained non-significant, due to large placebo-effect and wide inter-individual variation.

Ketamine as treatment for depression.

Ketamine infusions administered intravenously 1 to 3 times per week are the quickest and most effective treatment for depression. Short-course ketamine medication is established treatment both for unipolar depression and depressive episodes of bipolar affective disorder. Ketamine is suitable for initiating the treatment for treatment-resistant depression, alleviation of suicidal tendencies, and treatment of depressive patients suffering from simultaneous pain. The safety of prolonged treatment with ketamine is not known to sufficient degree. However, even long periods (up to 1.5 years) of ketamine treatment have not been associated with adverse effects. It would be appropriate to use short-course ketamine treatment more often than is currently done.

[Update on Current Care Guideline: Borderline personality disorder]. / Epävakaa persoonallisuus.

Borderline personality disorder is a severe disorder that increases disability to a considerable extent. Emotional instability, difficulties in regulating behavior and interpersonal relationships are essential features of the disorder. Borderline personality disorder has a more favorable course than previously thought. Dialectic behavioral therapy, cognitive therapy, mentalization therapy and transference-focused psychotherapy seem to be effective. Hospital treatment should be carried out primarily in day hospital settings. Antipsychotics and mood stabilizers may be used for a range of symptoms. SSRIs may be useful in the treatment of impulsivity and aggression. Benzodiazepines should be avoided.

Long-term benzodiazepine use and risk of labor market marginalization in Finland: A cohort study with 5-year follow-up.

BACKGROUND: Benzodiazepines and related drugs (BZDRs) are widely used in the treatment of anxiety and sleep disorders, but cognitive adverse effects have been reported in long-term use, and these may increase the risk of labor market marginalization (LMM). The aim of this study was to investigate whether the risk of LMM is associated with new long-term BZDR use compared to short-term use. METHODS: This register-based nationwide cohort study from Finland included 37,703 incident BZDR users aged 18-60 years who initiated BZDR use in 2006. During the first year of use, BZDR users were categorized as long-term users (≥180 days) versus short-term users based on PRE2DUP method. The main outcome was LMM, defined as receipt of disability pension, long-term sickness absence (>90 days), or long-term unemployment (>180 days). The risk of outcomes was analyzed with Cox regression models, adjusted with sociodemographic background, somatic and psychiatric morbidity, other types of medication and previous sickness absence. RESULTS: During 5 years of follow-up, long-term use (34.4%, N = 12,962) was associated with 27% (adjusted Hazard Ratio, aHR 1.27, 95% CI 1.23-1.31) increased risk of LMM compared with short-term use. Long-term use was associated with 42% (aHR 1.42, 95% CI 1.34-1.50) increased risk of disability pension and 26% increased risk of both long-term unemployment and long-term sickness absence. CONCLUSIONS: These results indicate that long-term use of BZDRs is associated with increased risk of dropping out from labor market. This may be partly explained by cognitive adverse effects of prolonged BZDR use, which should be taken into account when prescribing BZDRs.

[Treatment of drug-resistant depression]. / Lakeresistentin masennuksen hoito.

Depression is drug-resistant, if the severity of the symptoms has not decreased to half of the starting situation, despite appropriately conducted treatment with two antidepressants belonging to two different pharmacological categories. The incidence of drug-resistant depression in Finland is approximately 1%, and it is being treated too passively, whereby the number of disability pensions is rising. Current treatments include combinations of antidepressants, additional drugs for depression, psychotherapy, electrotherapy and serial magnetic stimulation. Ketamine infusions are also an effective, yet still experimental form of treatment.

Axis I and II psychiatric disorders in patients with traumatic brain injury: a 12-month follow-up study.

OBJECTIVE: To evaluate the occurrence of axis I and II psychiatric disorders among patients with traumatic brain injury (TBI). DESIGN: Prospective observational study. Forty-five adult patients, who had attended an emergency unit because of TBI, were recruited. At 12 months, 38 patients were interviewed. MEASURES: Psychiatric disorders were evaluated using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II). RESULTS: Before TBI, the 12-month rate of axis I psychiatric disorders was relatively high (39.5%) and the rate of alcohol dependence was especially elevated (18.4%). During the 12 months after TBI, axis I disorders were found in 47.4% of subjects. Six patients (15.8%) were found to have a disorder with an onset after TBI. Of these, five patients had depressive disorders (13.2%). Almost one third of the subjects (29.0%) had personality disorders. Antisocial and obsessive-compulsive personality disorders were the most frequent (10.5%). CONCLUSIONS: Both axis I and II psychiatric disorders are common among patients with TBI. Alcohol dependence and personality disorders are prevalent in individuals prone to TBI, whereas depressive disorders typically develop after injury. Psychiatric disorders should be addressed in rehabilitation, as otherwise they will hinder the recovery after TBI.

[Personality disorders and working capacity]. / Persoonallisuushäiriöt ja työkyky.

Personality disorders are common: some personality disorder is present in 6 to 10% of the populations. These disorders appear mostly together with some other psychiatric disorder which often has a larger impact on the working ability than the personality disorder. Because personality disorders appear particularly in interactive relationships, the patients may impose strain on their work community and jeopardize the working capacity of their workmates. Work itself is likely to improve the prognosis of personality disorders. Thus, for a person with personality disorder after losing his/her working capacity, primary objectives are active therapeutic approach, as short sick leave as possible and support for returning to work.

Successful suppression of musical hallucinations with low-frequency rTMS of the left temporo-parietal junction: A case report.

BACKGROUND: Inhibitory low frequency repetitive transcranial magnetic stimulation (rTMS) of the temporo-parietal area has been applied to treat both auditory verbal hallucinations as well as tinnitus. OBJECTIVE: We hypothesized that 1 Hz rTMS to the left temporoparietal junction (TPJ) may be beneficial in alleviating musical hallucinations (MH), another condition with auditory experiences in the absence of an external source. METHODS: Here we describe a patient with almost insufferable life-long MH with comorbid depression, who received inhibitory rTMS to the left TPJ as well as the right dorsolateral prefrontal cortex (DLPFC). RESULTS: The intrusiveness and frequency of her MH as well as her depressive symptoms alleviated quickly and substantially, and once-a-week maintenance therapy with rTMS seemed to preserve this amelioration. Future studies will hopefully reveal whether this is a viable treatment approach for other patients suffering from MH with or without comorbid depression.

Incidence of and Characteristics Associated With Long-term Benzodiazepine Use in Finland.

Importance: The proportion of patients who develop long-term benzodiazepine use remains controversial, as do the length of time before long-term use develops and the factors associated with long-term use. Objective: To investigate the incidence of long-term benzodiazepine and related drug (BZDR) use and factors associated with the development of long-term use implementing a follow-up design with new BZDR users. Design, Setting, and Participants: This population-based cohort study used a nationwide cohort of 129 732 new BZDR users in Finland. New users of BZDRs aged 18 years or older were identified from the prescription register maintained by the Social Insurance Institution of Finland as individuals who initiated BZDR use during 2006 and had not used BZDRs from 2004 to 2005. The follow-up continued until death, long-term hospitalization, a gap of 2 years in BZDR use, or December 31, 2015. The population was analyzed according to age at treatment initiation, categorized into younger (<65 years) and older (≥65 years) subcohorts. Analyses were conducted from May 2019 to February 2020. Exposures: Use of BZDRs, modeled from register-based data using the PRE2DUP (from prescriptions to drug use periods) method. Main Outcomes and Measures: Long-term BZDR use, defined as continuous use of 180 days or longer, and factors associated with long-term vs short-term use, compared using Cox proportional hazards models. Results: Among the 129 732 incident BZDR users, the mean (SD) age was 52.6 (17.7) years, and 78 017 (60.1%) individuals were women. During the follow-up period, 51 099 BZDR users (39.4%) became long-term users. Long-term treatment was more common in the older subcohort (19 103 individuals [54.5%]) than the younger subcohort (31 996 individuals [33.8%]). At 6 months, 28 586 individuals (22.0%) had become long-term users: 11 805 (33.7%) in the older subcohort and 16 781 (17.7%) in the younger subcohort. The largest proportions of initiators who became long-term users were those persons who initiated treatment with nitrazepam (76.4%; 95% CI, 73.6%-79.1%), temazepam (63.9%; 95% CI, 62.9%-65.0%), lorazepam (62.4%; 95% CI, 59.7%-65.1%), or clonazepam (57.5%; 95% CI, 55.9%-59.2%). Factors associated with the development of long-term use included male sex, older age, receipt of social benefits, psychiatric comorbidities, and substance abuse. Conclusions and Relevance: The findings of this population-based cohort study conducted in Finland suggest that the incidence of subsequent long-term BZDR use in individuals who initiate use of BZDRs is high, especially among older persons, and that the specific BZDR used initially is associated with the development of long-term BZDR use and should be carefully considered when prescribing BZDRs. The observed factors that appear to be associated with development of long-term BZDR use also should be considered in clinical decision-making when starting and monitoring BZDR treatment.

Attention and depressive symptoms in chronic phase after traumatic brain injury.

OBJECTIVE: To study whether attention deficits differ between TBI (traumatic brain injury) patients with and without depressive symptoms. METHOD: The study group (n = 61, mean age = 59 years) consisted of symptomatic TBI patients injured on average 30 years earlier. They were studied with a broad range of attention tasks including computerized methods. The patients were divided into those with depressive symptoms (n = 32) and those without (n = 29), according to the short form of the Beck depression scale with a cut-off score of 5. In addition, a diagnosis of major depression was applied according to the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) (n = 6). The groups with depression or depressive symptoms were compared with the non-depressed TBI patients and with an age- and education-matched healthy control group (n = 31). RESULTS: Cognitive methods that require flexibility (Trail making B, Card sorting, Word fluency) and working memory (Subtraction test) were sensitive to discriminate TBI patients without depressive symptoms from the control subjects (p < 0.001). Only a few methods were able to discriminate the TBI patients with depressive symptoms from those without (p < 0.001 for Simple reaction time, p < 0.003 for Vigilance test). The depressed TBI patients (assessed by SCAN) did not differ from the non-depressed TBI patients in attention functions. CONCLUSIONS: The results suggest that problems in complex attention processing are more specific to TBI, while slowness in simple psychomotor speed and impaired sustained attention may be mostly related to depressive symptoms in patients with chronic TBI sequelae.

Neuronavigated Versus Non-navigated Repetitive Transcranial Magnetic Stimulation for Chronic Tinnitus: A Randomized Study.

Repetitive transcranial magnetic stimulation (rTMS) has shown variable effect on tinnitus. A prospective, randomized 6-month follow-up study on parallel groups was conducted to compare the effects of neuronavigated rTMS to non-navigated rTMS in chronic tinnitus. Forty patients (20 men, 20 women), mean age of 52.9 years (standard deviation [ SD] = 11.7), with a mean tinnitus duration of 5.8 years ( SD = 3.2) and a mean tinnitus intensity of 62.2/100 ( SD = 12.8) on Visual Analog Scale (VAS 0-100) participated. Patients received 10 sessions of 1-Hz rTMS to the left temporal area overlying auditory cortex with or without neuronavigation. The main outcome measures were VAS scores for tinnitus intensity, annoyance, and distress, and Tinnitus Handicap Inventory (THI) immediately and at 1, 3, and 6 months after treatment. The mean tinnitus intensity (hierarchical linear mixed model: F3 = 7.34, p = .0006), annoyance ( F3 = 4.45, p = .0093), distress ( F3 = 5.04, p = .0051), and THI scores ( F4 = 17.30, p < .0001) decreased in both groups with non-significant differences between the groups, except for tinnitus intensity ( F3 = 2.96, p = .0451) favoring the non-navigated rTMS. Reduction in THI scores persisted for up to 6 months in both groups. Cohen's d for tinnitus intensity ranged between 0.33 and 0.47 in navigated rTMS and between 0.55 and 1.07 in non-navigated rTMS. The responder rates for VAS or THI ranged between 35% and 85% with no differences between groups ( p = .054-1.0). In conclusion, rTMS was effective for chronic tinnitus, but the method of coil localization was not a critical factor for the treatment outcome.

MRI findings and Axis I and II psychiatric disorders after traumatic brain injury: a 30-year retrospective follow-up study.

We studied the association between psychiatric disorders and the presence and location of traumatic lesions on magnetic resonance imaging (MRI) in 58 patients, on average, 30 years after traumatic brain injury. Axis I psychiatric disorders that had begun after the injury were assessed with the Schedules for Clinical Assessment in Neuropsychiatry (version 2.1), and Axis II disorders with the Structured Clinical Interview for DSM-III-R Personality Disorders. A 1.5-Tesla MRI scanner was used. One-third of the subjects had traumatic lesions visible on MRI. Only three psychiatric disorders, that is, delusional disorder, dementia, and the disinhibited type of organic personality syndrome, were significantly more common in subjects with contusions. Concerning the location of contusions, organic personality syndrome and its disinhibited subtype were associated with frontal lesions, and major depression was, surprisingly, inversely associated with temporal lesions. These results, which should be interpreted with caution due to the limited size of the study group, suggest that the majority of psychiatric disorders after traumatic brain injury are not closely related to the specific location or even the presence of contusions detectable with post-acute MRI.

The analgesic effect of therapeutic rTMS is not mediated or predicted by comorbid psychiatric or sleep disorders.

BACKGROUND: Mechanisms underlying alleviation of neuropathic pain by repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) and right secondary somatosensory cortex (S2) are only partly known. Patients with chronic neuropathic pain often have comorbidities like depression and sleep problems. Through functional connectivity, rTMS of M1 and S2 may activate dorsolateral prefrontal cortex, the target for treating depression with rTMS. Thus, the analgesic effect of rTMS could be mediated indirectly via improvement of psychiatric comorbidities or sleep. We examined whether rTMS has an independent analgesic effect or whether its clinical benefits depend on effects on mood or sleep. We also evaluated if comorbid psychiatric or sleep disorders predict the treatment outcome. METHODS: Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized controlled crossover rTMS study. Patients' psychiatric history was evaluated by a specialist in psychiatry. Intensity and interference of pain, mood, and the quality of sleep and life were evaluated at baseline and after 2 active (primary somatosensory cortex [S1]/M1 and S2) and placebo rTMS treatments. A logistic regression analysis was done to investigate predictors of treatment outcome. RESULTS: The analgesic effect of the right S2 stimulation was not associated with improvement of psychiatric conditions or sleep, whereas S1/M1 stimulation improved sleep without significant analgesic effect (P = 0.013-0.046 in sleep scores). Psychiatric and sleep disorders were more common in patients than in the general population (P = 0.000-0.001 in sleep scores), but these comorbidities did not predict the rTMS treatment outcome. CONCLUSION: We conclude that rTMS to the right S2 does not exert its beneficial analgesic effects in chronic neuropathic orofacial pain via indirect improvement of comorbid psychiatric or sleep disorders.

Alexithymia after traumatic brain injury: its relation to magnetic resonance imaging findings and psychiatric disorders.

OBJECTIVE: People with traumatic brain injury (TBI) were studied to assess the prevalence of alexithymia and its relationship to magnetic resonance imaging (MRI) findings and psychiatric disorders. METHODS: Fifty-four participants, 67% men, were evaluated after a median of 30 years since TBI. A control group was matched for age, gender, and severity of depression. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20). In patients with TBI, axis I psychiatric disorders were assessed with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN, version 2.1), and axis II disorders with the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II). MRI examinations were carried out with a 1.5 T MRI scanner. RESULTS: Alexithymia was significantly more common in patients with TBI than in controls (31.5% versus 14.8%; odds ratio 2.64, 95% confidence interval 1.03-6.80). None of the variables representing TBI, ie, severity of TBI or the presence, laterality, or location of contusions on MRI, was associated with the TAS-20 total scores. Several current axis I and II psychiatric disorders, particularly organic personality syndrome, were connected to higher TAS-20 scores. CONCLUSION: Alexithymia is common, along with psychiatric disorders, in patients with TBI. Both of them may reflect dysfunction of the injured brain. In clinical practice, alexithymic features should be taken into consideration in psychosocial rehabilitation after TBI.

Right secondary somatosensory cortex-a promising novel target for the treatment of drug-resistant neuropathic orofacial pain with repetitive transcranial magnetic stimulation.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex has analgesic effect; however, the efficacy of other cortical targets and the mode of action remain unclear. We examined the effects of rTMS in neuropathic orofacial pain, and compared 2 cortical targets against placebo. Furthermore, as dopaminergic mechanisms modulate pain responses, we assessed the influence of the functional DRD2 gene polymorphism (957C>T) and the catechol-O-methyltransferase (COMT) Val158Met polymorphism on the analgesic effect of rTMS. Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized, placebo-controlled, crossover study. Navigated high-frequency rTMS was given to the sensorimotor (S1/M1) and the right secondary somatosensory (S2) cortices. All subjects were genotyped for the DRD2 957C>T and COMT Val158Met polymorphisms. Pain, mood, and quality of life were monitored throughout the study. The numerical rating scale pain scores were significantly lower after the S2 stimulation than after the S1/M1 (P = 0.0071) or the sham (P = 0.0187) stimulations. The Brief Pain Inventory scores were also lower 3 to 5 days after the S2 stimulation than those at pretreatment baseline (P = 0.0127 for the intensity of pain and P = 0.0074 for the interference of pain) or after the S1/M1 (P = 0.001 and P = 0.0001) and sham (P = 0.0491 and P = 0.0359) stimulations. No correlations were found between the genetic polymorphisms and the analgesic effect in the present small clinical sample. The right S2 cortex is a promising new target for the treatment of neuropathic orofacial pain with high-frequency rTMS.

Axis I and II psychiatric disorders after traumatic brain injury: a 30-year follow-up study.

OBJECTIVE: Patients who had suffered traumatic brain injury were evaluated to determine the occurrence of psychiatric disorders during a 30-year follow-up. METHOD: Sixty patients were assessed on average 30 years after traumatic brain injury. DSM-IV axis I disorders were diagnosed on a clinical basis with the aid of the Schedules for Clinical Assessment in Neuropsychiatry (version 2.1), and axis II disorders were diagnosed with the Structured Clinical Interview for DSM-III-R Personality Disorders. Cognitive impairment was measured with a neuropsychological test battery and the Mini-Mental State Examination. RESULTS: Of the 60 patients, 29 (48.3%) had had an axis I disorder that began after traumatic brain injury, and 37 (61.7%) had had an axis I disorder during their lifetimes. The most common novel disorders after traumatic brain injury were major depression (26.7%), alcohol abuse or dependence (11.7%), panic disorder (8.3%), specific phobia (8.3%), and psychotic disorders (6.7%). Fourteen patients (23.3%) had at least one personality disorder. The most prevalent individual disorders were avoidant (15.0%), paranoid (8.3%), and schizoid (6.7%) personality disorders. Nine patients (15.0%) had DSM-III-R organic personality syndrome. CONCLUSIONS: The results suggest that traumatic brain injury may cause decades-lasting vulnerability to psychiatric illness in some individuals. Traumatic brain injury seems to make patients particularly susceptible to depressive episodes, delusional disorder, and personality disturbances. The high rate of psychiatric disorders found in this study emphasizes the importance of psychiatric follow-up after traumatic brain injury.

Altered dopamine D2 receptor binding in atypical facial pain.

Animal studies suggest that the dopaminergic system plays a role in central pain modulation. We have previously demonstrated with positron emission tomography (PET) that striatal dopaminergic hypofunction may be involved in the burning mouth syndrome. The aim of the present study was to evaluate the nigrostriatal dopaminergic system in patients with atypical facial pain using PET. In seven patients with atypical facial pain, striatal presynaptic dopaminergic function was assessed with [18F]FDOPA and dopamine D1 and D2 receptor availabilities with [11C]NNC 756 and [11C]raclopride, respectively. The results were compared with those of healthy controls. A quantitative region-of-interest analysis showed that the uptakes of [18F]FDOPA and [11C]NNC 756 did not differ between patients and controls. There was a tendency of increased D2 receptor availability in the left putamen (P=0.056), and the D1/D2 ratio in the putamen was decreased bilaterally by 7.7% (P=0.002) in patients when compared to controls. In a voxel-based analysis, the uptake of [11C]raclopride was increased in the left putamen (P=0.025). In conclusion, the increase in D2 receptor availability in the left putamen and the decrease in D1/D2 ratio imply that alterations in the striatal dopaminergic system as evaluated by PET may be involved in chronic orofacial pain conditions.

Striatal dopamine D1 and D2 receptors in burning mouth syndrome.

Animal studies have indicated that the nigrostriatal dopaminergic system is involved in central pain modulation. In a recent positron emission tomography (PET) study, we demonstrated presynaptic dysfunction of the nigrostriatal dopaminergic pathway in burning mouth syndrome, which is a chronic pain state. The objective of the present study was to examine striatal dopamine D1 and D2 receptors in these patients. We used 11C-NNC 756 and 11C-raclopride to study D1 and D2 receptor binding in a PET study in ten burning mouth patients and 11 healthy controls. Patients underwent a structured psychiatric evaluation and an electrophysiological test for the excitability of the blink reflex. The striatal uptake of 11C-NNC 756 did not differ between patients and controls. In a voxel-level analysis, the uptake of 11C-raclopride was statistically significantly higher in the left putamen in burning mouth patients (corrected P-value 0.038 at cluster-level). In the region of interest analysis, the D1/D2 ratio was 7.7% lower in the right putamen (0.64+/-0.04 vs. 0.69+/-0.04, P=0.01) and 6.4 % lower in the left putamen (0.65+/-0.05 vs. 0.70+/-0.05, P=0.05) when compared to controls. Increased 11C-raclopride uptake and the subsequent decrease in the D1/D2 ratio may indicate a decline in endogenous dopamine levels in the putamen in burning mouth patients.