•High clinical pain intensity is not the sole determinant of opioid craving.•Opioid withdrawal symptoms contribute to opioid craving in patients with pain.•Opioid withdrawal symptoms contribute to ...higher negative affect and catastrophizing.•Psychological distress mediates the link between withdrawal symptoms and craving.
Research has shown that opioid craving is one of the strongest determinants of opioid misuse in patients with chronic pain. To date, however, little is known on the factors that contribute to opioid craving in these patients. It is possible that patients’ physical dependence to opioids, manifested by opioid withdrawal symptoms in between daily opioid doses, contribute to opioid craving. Physical dependence symptoms might also lead to psychological distress, which in turn might contribute to opioid craving. The first objective of this study was to examine the day-to-day association between opioid withdrawal symptoms and opioid craving among patients with chronic pain. We also examined whether negative affect and catastrophic thinking mediated this association.
In this longitudinal study, chronic pain patients (n = 79) prescribed short-acting opioids completed daily diaries for 14 consecutive days. Diaries assessed a host of pain, psychological, and opioid-related variables.
Day-to-day elevations in opioid withdrawal symptoms were associated with heightened opioid craving (p < .001). Results of a multilevel mediation analysis revealed that this association was mediated by patients’ daily levels of negative affect and catastrophizing (p < .001).
Our study provides valuable new insights into our understanding of factors that may contribute to prescription opioid craving among patients with chronic pain.
Dopamine and Addiction Wise, Roy A; Robble, Mykel A
Annual review of psychology,
01/2020, Letnik:
71, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Addiction is commonly identified with habitual nonmedical self-administration of drugs. It is usually defined by characteristics of intoxication or by characteristics of withdrawal symptoms. Such ...addictions can also be defined in terms of the brain mechanisms they activate; most addictive drugs cause elevations in extracellular levels of the neurotransmitter dopamine. Animals unable to synthesize or use dopamine lack the conditioned reflexes discussed by Pavlov or the appetitive behavior discussed by Craig; they have only unconditioned consummatory reflexes. Burst discharges (phasic firing) of dopamine-containing neurons are necessary to establish long-term memories associating predictive stimuli with rewards and punishers. Independent discharges of dopamine neurons (tonic or pacemaker firing) determine the motivation to respond to such cues. As a result of habitual intake of addictive drugs, dopamine receptors expressed in the brain are decreased, thereby reducing interest in activities not already stamped in by habitual rewards.
What is known and objective
Opioid use in the United States has reached unprecedented—some would even say crisis—levels. Although many individuals use opioid drugs as part of legitimate pain ...management plans, a significant number misuse prescription or illicit opioids. With regular opioid use, individuals develop tolerance and physical dependence; both are predictable, physiologic responses to repeated opioid exposure. However, a substantial number of individuals who misuse opioids will develop opioid use disorder (OUD), a complex, primary, chronic, neurobiological disease rooted in genetic, environmental and psychosocial factors. This article discusses OUD, opioid receptor physiology, and opioid withdrawal symptomatology and pathophysiology, as well as current treatment options available to reduce opioid withdrawal symptoms in individuals with physical dependence and/or OUD.
Methods
The research articles regarding OUD and its management have been reviewed thoroughly based on a PubMed literature search using keywords related to opioid dependence, its pathophysiology and current treatment strategies.
Results and discussion
Tolerance/physical dependence and the behavioural characteristics associated with OUD reflect complex neurobiologic adaptations in several major systems of the brain, including the locus ceruleus and mesolimbic systems. Physical dependence is responsible for the distressing withdrawal symptoms individuals experience upon abrupt cessation or rapid dose reduction of exogenous opioids. Opioid withdrawal symptoms are a key driver behind continued opioid use, and a barrier to opioid discontinuation. Several opioid‐based medications are available to treat patients with OUD; these treatments can diminish opioid withdrawal symptoms and cravings as well as block opioid effects in the event of relapse. Additionally, non‐opioid drugs may be used during acute detoxification to help alleviate opioid withdrawal symptoms.
What is new and conclusion
The opioid crisis has produced many challenges for physicians, one being the need to determine which patients would benefit most from maintenance therapy and which may be candidates for opioid discontinuation. In addition to summarizing current understanding of OUD, we provide a new algorithm for determining the need for continued opioid use as well as examples of situations where management of opioid withdrawal symptoms is indicated.
Opioid abuse has reached epidemic levels and includes many chronic pain patients. This review discusses opioid receptor physiology and opioid withdrawal symptomatology and pathophysiology, as well as current treatment options available to assist in the withdrawal process in individuals with physical dependence and/or opioid use disorder.
Background: Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim of this paper is ...to identify the occurrence, frequency, and features of withdrawal symptoms after SNRI discontinuation. Methods: PRISMA guidelines were followed to conduct a systematic review. Electronic databases included PubMed, the Cochrane Library, Web of Science, and MEDLINE from the inception of each database to June 2017. Titles, abstracts, and topics were searched using a combination of the following terms: “duloxetine” OR “venlafaxine” OR “desvenlafaxine” OR “milnacipran” OR “levomilnacipran” OR “SNRI” OR “second generation antidepressant” OR “serotonin norepinephrine reuptake inhibitor” AND “discontinuation” OR “withdrawal” OR “rebound.” Only published trials in the English language were included. Results: Sixty-one reports met the criteria for inclusion. There were 22 double-blind randomized controlled trials, 6 studies where patients were treated in an open fashion and then randomized to a double-blind controlled phase, 8 open trials, 1 prospective naturalistic study, 1 retrospective study, and 23 case reports. Withdrawal symptoms occurred after discontinuation of any type of SNRI. The prevalence of withdrawal symptoms varied across reports and appeared to be higher with venlafaxine. Symptoms typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well. Conclusions: Clinicians need to add SNRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with other types of psychotropic drugs. The results of this study challenge the use of SNRI as first-line treatment for mood and anxiety disorders.
Despite the widespread use of glucocorticoids in inflammatory and autoimmune disorders, there is uncertainty about the safe cessation of long-term systemic treatment, as data from prospective trials ...are largely missing. Due to potential disease relapse or glucocorticoid-induced hypocortisolism, the drug is often tapered to sub-physiological doses rather than stopped when the underlying disease is clinically stable, increasing the cumulative drug exposure. Conversely, the duration of exposure to glucocorticoids should be minimized to lower the risk of side effects. We designed a multicenter, randomized, triple-blinded, placebo-controlled trial to test the clinical noninferiority of abrupt glucocorticoid stop compared to tapering after greater than or equal to28 treatment days with greater than or equal to420 mg cumulative and greater than or equal to7.5 mg mean daily prednisone-equivalent dose. 573 adult patients treated systemically for various disorders will be included after their underlying disease has been stabilized. Prednisone in tapering doses or matching placebo is administered over 4 weeks. A 250 mg ACTH-test, the result of which will be revealed a posteriori, is performed at study inclusion; all patients are instructed on glucocorticoid stress cover dosing. Follow-up is for 6 months. The composite primary outcome measure is time to hospitalization, death, initiation of unplanned systemic glucocorticoid therapy, or adrenal crisis. Secondary outcomes include the individual components of the primary outcome, cumulative glucocorticoid doses, signs and symptoms of hypocortisolism, and the performance of the ACTH test in predicting the clinical outcome. Cox proportional hazard, linear, and logistic regression models will be used for statistical analysis. This trial aims to demonstrate the clinical noninferiority and safety of abrupt treatment cessation after greater than or equal to28 days of systemic glucocorticoid therapy in patients with stabilized underlying disease.
Plasticity of neurons in the ventral tegmental area (VTA) is critical for establishment of drug dependence. However, the remodeling of the circuits mediating the transition between positive and ...negative effect remains unclear. Here, we used neuronal activity-dependent labeling technique to characterize and temporarily control the VTA neuronal ensembles recruited by the initial morphine exposure (morphine-positive ensembles, Mor-Ens). Mor-Ens preferentially projected to NAc, and induced dopamine-dependent positive reinforcement. Electrophysiology and rabies viral tracing revealed the preferential connections between the VTA-projective corticotrophin-releasing hormone (CRH) neurons of central amygdala (CRH.sup.CeAright arrowVTA) and Mor-Ens, which was enhanced after escalating morphine exposure and mediated the negative effect during opiate withdrawal. Pharmacologic intervention or CRISPR-mediated repression of CRHR1 in Mor-Ens weakened the inhibitory CRH.sup.CeAright arrowVTA inputs, and alleviated the negative effect during opiate withdrawal. These data suggest that neurons encoding opioid reward experience are inhibited by enhanced CRH.sup.CeAright arrowVTA inputs induced by chronic morphine exposure, leading to negative effect during opiate withdrawal, and provide new insight into the pathological changes in VTA plasticity after drug abuse and mechanism of opiate dependence.
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