A study of psychological pain in substance use disorder and its relationship to treatment outcome.

Substance Use Disorder (SUD) is a major public health concern affecting an estimated 22.5 million individuals in the United States. The primary aim of this study was to characterize psychological pain in a cohort of patients participating in outpatient treatment for SUD. A secondary aim was to determine the relationships between pre-treatment assessments of psychological pain, depression, anxiety and hopelessness with treatment retention time and completion rates. Data was analyzed from 289 patients enrolled in an outpatient community drug treatment clinic in Southern California, U.S. A previously determined threshold score on the Mee-Bunney Psychological Pain Assessment Scale (MBP) was utilized to group patients into high and low-moderate scoring subgroups. The higher pain group scored higher on measures of anxiety, hopelessness and depression compared to those in the low-moderate pain group. Additionally, patients scoring in the higher psychological pain group exhibited reduced retention times in treatment and more than two-fold increased odds of dropout relative to patients with lower pre-treatment levels of psychological pain. Among all assessments, the correlation between psychological pain and treatment retention time was strongest. To our knowledge, this is the first study to demonstrate that psychological pain is an important construct which correlates with relevant clinical outcomes in SUD. Furthermore, pre-treatment screening for psychological pain may help target higher-risk patients for clinical interventions aimed at improving treatment retention and completion rates.

Assessment of psychological pain in suicidal veterans.

Psychological pain is a relatively understudied and potentially important construct in the evaluation of suicidal risk. Psychological pain also referred to as 'mental pain' or 'psychache' can be defined as an adverse emotional reaction to a severe trauma (e.g., the loss of a child) or may be associated with an illness such as depression. When psychological pain levels reach intolerable levels, some individuals may view suicide as the only and final means of escape. To better understand psychological pain, we previously developed and validated a brief self-rating 10-item scale, Mee-Bunney Psychological Pain Assessment Scale [MBP] in depressed patients and non-psychiatric controls. Our results showed a significant increase in psychological pain in the depressed patients compared to controls. We also observed a significant linear correlation between psychological pain and suicidality in the depressed patient cohort. The current investigation extends our study of psychological pain to a diagnostically heterogeneous population of 57 US Veterans enrolled in a suicide prevention program. In addition to the MBP, we administered the Columbia Suicide Severity Rating Scale (C-SSRS), Beck Depression Inventory (BDI-II), Beck Hopelessness Scale (BHS), and the Barratt Impulsiveness Scale (BIS-11). Suicidal patients scoring above a predetermined threshold for high psychological pain also had significantly elevated scores on all the other assessments. Among all of the evaluations, psychological pain accounted for the most shared variance for suicidality (C-SSRS). Stepwise regression analyses showed that impulsiveness (BIS) and psychological pain (MBP) contributed more to suicidality than any of the other combined assessments. We followed patients for 15 months and identified a subgroup (24/57) with serious suicide events. Within this subgroup, 29% (7/24) had a serious suicidal event (determined by the lethality subscale of the C-SSRS), including one completed suicide. Our results build upon our earlier findings and recent literature supporting psychological pain as a potentially important construct. Systematically evaluating psychological pain along with additional measures of suicidality could improve risk assessment and more effectively guide clinical resource allocation toward prevention.

Psychological pain: a review of evidence.

This paper defines a symptom construct termed psychological pain and reviews clinical and neuroimaging evidence relevant to it. The psychological pain associated with severe depression is often perceived as worse than any physical pain that the individual has experienced and could be a critical component of suicidality that could be systematically assessed in potentially suicidal patients. Converging evidence from brain imaging studies suggests overlapping patterns of brain activation induced by both psychological pain and by physical pain. Future research on the role of psychological pain and its interaction with nociceptive pathways may provide novel clues to the understanding and treatment of depression and other psychiatric illnesses.

Assessment of psychological pain in major depressive episodes.

Severe psychological or mental pain is defined as an experience of unbearable torment which can be associated with a psychiatric illness (e.g., major depressive disorder) or a tragic loss such as the death of a child. A brief self-rating scale (Mee-Bunney Psychological Pain Assessment Scale [MBPPAS]) was developed to assess the intensity of psychological pain. The scale was used to measure psychological pain in 73 major depressive episode (MDE) patients and 96 non-psychiatric controls. In addition to the MBPPAS, all subjects completed four additional instruments: Suicidal Behavior Questionnaire (SBQ), Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), and the Brief Pain Inventory (BPI). Known-groups, content and convergent validity, and internal reliability of the scale were established. MDE and control subjects were ranked according to MBPPAS scores. A threshold was set at 32 representing 0.5 SD above the mean for MDEs. MDE subjects above the threshold of 32 had significantly higher SBQ scores than those below. A significant linear correlation between psychological pain and SBQ suicidality scores was observed. This is the first study to contrast psychological pain in controls and patients with MDE. Our results suggest that psychological pain is a useful and unique construct in patients with MDE that can be reliably assessed and may aid in the evaluation of suicidal risk.

Novelty seeking and the dopamine D4 receptor gene (DRD4) revisited in Asians: haplotype characterization and relevance of the 2-repeat allele.

The relationship of the dopamine D4 receptor gene (DRD4) to the behavioral trait of novelty seeking has not been uniformly consistent. A methodological shortcoming in previous studies may relate to the way different DRD4 variants were categorized. Because of evolutionary and functional (e.g., diminished potency to reduce cAMP) similarities between the 2- and 7-repeat (2R, 7R) alleles of the DRD4, we suggest grouping of these two alleles together may facilitate detection of biologically meaningful and reproducible association findings with behavioral traits. We measured novelty seeking with the Tridimensional Personality Questionnaire (TPQ) in a community sample of Caucasian, Korean, and Filipino subjects (N = 171) who were subsequently characterized for the DRD4 variable number of tandem repeats (VNTR). In the Korean sample, those with a 2R and/or 7R allele scored significantly higher on novelty seeking scale (P < 0.05). By contrast, grouping the VNTR alleles by size (2, 3, 4 vs. 5, 6, 7), as has been done in similar studies of Asian subjects, was not significant. Using the extreme discordant phenotype (EDP) strategy in the pooled sample and selecting the individuals within the upper and lower decile, we observed a trend for association with higher novelty seeking in individuals who carry the 2R and/or 7R alleles (P = 0.06). We also confirmed that the 2R allele in the Korean and Filipino subjects was the result of a one-step recombination event between the 4R and 7R alleles. This study suggests that genetic association analyses can benefit by consideration of the shared functional and evolutionary attributes of the DRD4 2R and 7R alleles.

Pharmacogenetics for off-patent antipsychotics: reframing the risk for tardive dyskinesia and access to essential medicines.

First-generation antipsychotics (FGAs) induce tardive dyskinesia, a debilitating involuntary hyperkinetic movement disorder, in 20-50% of individuals with a psychotic illness during chronic treatment. There is presently no curative treatment or definitive predictive test for tardive dyskinesia. The authors note that the three antipsychotic drugs enlisted in the most recent (14th) World Health Organization Model List of Essential Medicines--chlorpromazine, fluphenazine and haloperidol--belong to the FGA therapeutic class. In this regard, the need to choose between the competing objectives of ensuring global access to affordable and efficacious medicines, such as FGAs, and the formidable long-term risk for tardive dyskinesia, may create an ethical conundrum. Pharmacogenetics has thus far been conceptually framed as a tool to individualize therapy with new drugs under patent protection. However, the authors suggest that pharmacogenetics may also improve access to pharmacotherapy through the reintroduction of affordable second-line generic drugs or FGAs with suboptimal safety, as first-line therapy, in targeted subpopulations in whom they present a lower risk for tardive dyskinesia. To impact positively on global public health and distributive justice, a directory complementary to the essential medicines library--one that enlists the 'essential biomarkers' required for optimal pharmacotherapy--may benefit patients who do not have adequate access to new antipsychotic medications. This review discusses pharmacogenetic associations of tardive dyskinesia that are in part supported by meta-analyses and the oxidative stress-neuronal degeneration hypothesis.