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Georgian Medical News Sep 2023The aim of this study was to evaluate current approaches to the pharmacotherapy of posttraumatic stress disorder. An information search was carried out in the databases...
The aim of this study was to evaluate current approaches to the pharmacotherapy of posttraumatic stress disorder. An information search was carried out in the databases PubMed, Ovid, EMBASE by keywords: "posttraumatic stress disorder", "treatment", and "medications". Search depth 2012-2022 years. From the general data (4877 articles) there were selected 14 articles with the highest degree of relevance. A content analysis of selected articles was carried out with the formation of recommendations for the use of pharmacotherapy in posttraumatic stress disorder. Currently, there are no unified approaches to the pharmacotherapy of posttraumatic stress disorder. Antidepressants (SSRI SNRIs) are primarily considered as first-line drugs, but only sertraline, paroxetine, and fluoxetine are approved by the FDA. But these drugs have a fairly wide range of side effects, including suicidal thoughts. The use of benzodiazepines should be limited as they increase the risk of developing posttraumatic stress disorder. Vortioxetine becomes a very promising option. The most significant benefits of vortioxetine are the significant positive effects of vortioxetine on attention, memory, and executive function. There is some evidence for the use of alpha-1 adrenoceptor antagonists and alpha-2 adrenoceptor agonists in therapy. In insomnia the use of prazosin and trazodone is recommended. Pharmacotherapy of posttraumatic stress disorder requires administration of medications with multimodal action. Currently, there are no unified approaches to the pharmacotherapy of posttraumatic stress disorder. Further randomized clinical trials are necessary for developing effective treatment of posttraumatic stress disorder.
Topics: Humans; Antidepressive Agents; Receptors, Adrenergic; Stress Disorders, Post-Traumatic; Vortioxetine
PubMed: 37991966
DOI: No ID Found -
Frontiers in Pharmacology 2024This study aimed to investigate the plasma and breastmilk concentrations for sertraline, citalopram and paroxetine for assessment of the Milk/Plasma (M/P) ratio and...
OBJECTIVES
This study aimed to investigate the plasma and breastmilk concentrations for sertraline, citalopram and paroxetine for assessment of the Milk/Plasma (M/P) ratio and Absolute Infant Dose (AID), and to determine actual infant drug exposure through breastfeeding. Subsequently, informed recommendations will be formulated regarding the advisability of breastfeeding in women undergoing treatment with the three most widely used antidepressants.
METHODS
A pharmacokinetic study in lactating women and their infants using sertraline, citalopram or paroxetine was performed. Paired breastmilk and plasma samples and single point infant plasma samples were collected to determine antidepressant concentrations. An Area Under the Curve (AUC) based approach with the trapezoidal rule was used to calculate M/P ratios and AID for all three antidepressants by combining all measured concentrations for the same dose.
RESULTS
Thirty-seven lactating women and their infants participated in this study. 111 paired breastmilk and plasma samples and 37 single point infant plasma samples were collected. Detectable concentrations of sertraline, citalopram and paroxetine were present in all breastmilk samples. For sertraline and citalopram M/P ratio is above one, indicating higher breastmilk than plasma concentrations, however, drug exposure by breastmilk did not lead to detectable plasma drug levels in any of the 15 infants for sertraline, for nine (out of 13) infants for citalopram and for eight (out of nine) infants for paroxetine.
CONCLUSION
Given the well-known benefits of breastfeeding, our findings support breastfeeding of infants by mothers who are taking sertraline, citalopram or paroxetine is safe. Sertraline and paroxetine are the preferred antidepressants during breastfeeding, reaching mostly undetectable infant drug levels.
PubMed: 38841362
DOI: 10.3389/fphar.2024.1414677 -
Focus (American Psychiatric Publishing) Jul 2023Unsuccessfully treated posttraumatic stress disorder (PTSD) is a serious and life-threatening disorder. Two medications, paroxetine hydrochloride and sertraline... (Review)
Review
Unsuccessfully treated posttraumatic stress disorder (PTSD) is a serious and life-threatening disorder. Two medications, paroxetine hydrochloride and sertraline hydrochloride, are approved treatments for PTSD by the Food and Drug Administration (FDA). Analyses of pharmacotherapies for PTSD found only small to moderate effects when compared with placebo. The Multidisciplinary Association for Psychedelic Studies (MAPS) obtained Breakthrough Therapy Designation (BTD) from the FDA for 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD on the basis of pooled analyses showing a large effect size for this treatment. This review covers data supporting BTD. In this treatment, MDMA is administered with psychotherapy in up to three monthly 8-h sessions. Participants are prepared for these sessions beforehand, and process material arising from the sessions in follow-up integrative psychotherapy sessions. Comparing data used for the approval of paroxetine and sertraline and pooled data from Phase 2 studies, MAPS demonstrated that MDMA-assisted psychotherapy constitutes a substantial improvement over available pharmacotherapies in terms of safety and efficacy. Studies of MDMA-assisted psychotherapy had lower dropout rates compared to sertraline and paroxetine trials. As MDMA is only administered under direct observation during a limited number of sessions, there is little chance of diversion, accidental or intentional overdose, or withdrawal symptoms upon discontinuation. BTD status has expedited the development of MAPS phase 3 trials occurring worldwide, leading up to a planned submission seeking FDA approval in 2021. Appeared originally in ; .
PubMed: 37404974
DOI: 10.1176/appi.focus.23021013 -
Acta Psychiatrica Scandinavica May 2024Long-term studies comparing nonresponse to antidepressants for major depressive disorder (MDD) are lacking. (Comparative Study)
Comparative Study
Comparative responses to 17 different antidepressants in major depressive disorder: Results from a 2-year long-term nation-wide population-based study emulating a randomized trial.
BACKGROUND
Long-term studies comparing nonresponse to antidepressants for major depressive disorder (MDD) are lacking.
AIMS
To present systematic population-based nation-wide register data on comparative 2-year non-response within six antidepressant drug classes and 17 different antidepressants in patients with MDD.
METHOD
The study included all 106,920 patients in Denmark with a first main index diagnosis of MDD at a psychiatric hospital inpatient or outpatient contact and who subsequently had a purchase of an antidepressant in the period from 1995 to 2018. Non-response to first antidepressant within a 2-year study period was defined as switch to or add-on of another antidepressant, antipsychotic medication, lithium, or hospitalization. Analyses emulated a targeted trial in populations standardized according to age, sex, socioeconomic status, and comorbidity with psychiatric and physical disorders.
RESULTS
Compared with sertraline, there was no difference for citalopram (RR: 1.00 [95% CI: 0.98-1.02]) but fluoxetine (1.13 [95% CI: 1.10-1.17]), paroxetine (1.06 [95% CI: 1.01-1.10]) and escitalopram (1.22 [95% CI: 1.18-1.25]) were associated with higher risk ratio of non-responses. Within selective noradrenaline reuptake inhibitors, sertraline outperformed reboxetine; within serotonin-norepinephrine reuptake inhibitors, venlafaxine outperformed duloxetine; within noradrenergic and specific serotonergic antidepressants, mirtazapine outperformed mianserin and within the class of other antidepressants, sertraline outperformed agomelatine and vortioxetine. Within tricyclic antidepressants, compared to amitriptyline, nortriptyline, dosulepin, and clomipramine had higher non-response, whereas there was no difference for imipramine.
CONCLUSIONS
These analyses emulating a randomized trial of "real world" observational register-based data show that 2-year long-term non-responses to some antidepressants within six different drug classes are increased over others.
Topics: Humans; Antidepressive Agents; Depressive Disorder, Major; Fluoxetine; Selective Serotonin Reuptake Inhibitors; Sertraline
PubMed: 38379028
DOI: 10.1111/acps.13673 -
Psychological Medicine Jul 2023Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been... (Review)
Review
BACKGROUND
Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been shown. However, there have been few attempts to incorporate data on subjective experiences under different AD.
METHOD
We conducted a qualitative and quantitative analysis of the posts from the website www.askapatient.com from different AD. We reviewed a random sample of 1000 posts.
RESULT
After applying the inclusion and exclusion criteria, we included a final sample of 450 posts, 50 on each of the most used AD: sertraline, citalopram, paroxetine, escitalopram, fluoxetine, venlafaxine, duloxetine, mirtazapine, and bupropion. Bupropion, citalopram, and venlafaxine had the higher overall satisfaction ratings. Sertraline, paroxetine, and fluoxetine had high reports of emotional blunting, while bupropion very few. Overall satisfaction with AD treatment was inversely associated with the presence of the following side-effects: suicidality, irritability, emotional blunting, cognitive disturbances, and withdrawal symptoms. After adjusting for confounders, only emotional blunting was shown to be more frequently reported by users of serotonergic agents, as compared to non-serotoninergic agents.
CONCLUSION
This research points out that the subjective experience of patients under treatment should be taken into consideration when selecting an AD as differences between agents were evident. In contrast to the more frequent treatment decisions, users might prefer receiving a non-serotoninergic agent over a serotonergic one due to their lower propensity to produce emotional blunting.
Topics: Humans; Venlafaxine Hydrochloride; Citalopram; Paroxetine; Fluoxetine; Bupropion; Sertraline; Antidepressive Agents
PubMed: 35346413
DOI: 10.1017/S0033291722000678 -
Current Topics in Behavioral... Nov 2023SSRIs are one of the most widely used drug therapies in primary care and psychiatry, and central to the management of the most common mental health problems in today's...
SSRIs are one of the most widely used drug therapies in primary care and psychiatry, and central to the management of the most common mental health problems in today's society. Despite this, SSRIs suffer from a slow onset of therapeutic effect and relatively poor efficacy as well as adverse effects, with recent concerns being focused on a disabling SSRI discontinuation syndrome. The mechanism underpinning their therapeutic effect has long shifted away from thinking that SSRIs act simply by increasing 5-HT in the synapse. Rather, a current popular view is that increased 5-HT is just the beginning of a series of complex downstream signalling events, which trigger changes in neural plasticity at the functional and structural level. These changes in plasticity are then thought to interact with neuropsychological processes to enhance re-learning of emotional experiences that ultimately brings about changes in mood. This compelling view of SSRI action is underpinning attempts to understand fast-acting antidepressants, such as ketamine and psychedelic drugs, and aid the development of future therapies. An important gap in the theory is evidence that changes in plasticity are causally linked to relevant behavioural effects. Also, predictions that the SSRI-induced neural plasticity might have applicability in other areas of medicine have not yet been borne out. In contrast to the sophisticated view of the antidepressant action of SSRIs, the mechanism underpinning SSRI discontinuation is little explored. Nevertheless, evidence of rebound increases in 5-HT neuron excitability immediately on cessation of SSRI treatment provide a starting point for future investigation. Indeed, this evidence allows formulation of a mechanistic explanation of SSRI discontinuation which draws on parallels with the withdrawal states of other psychotropic drugs.
PubMed: 37955823
DOI: 10.1007/7854_2023_452 -
The American Journal of Psychiatry Jan 2024The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing...
OBJECTIVE
The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes.
METHODS
This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders.
RESULTS
The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50-1.61; venlafaxine: IRR=1.22, 95% CI=1.12-1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15-1.81; venlafaxine: IRR=1.47, 95% CI=1.20-1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertraline users. These results remained consistent in analyses stratified by sex and age (≤75 years vs. >75 years).
CONCLUSIONS
This real-world evidence suggests that clinical outcomes may vary among initiators of commonly used antidepressants in older adults, which may inform benefit-risk evaluation at treatment initiation, and highlights the importance of careful selection of antidepressant treatment.
Topics: Female; Humans; Aged; Male; Venlafaxine Hydrochloride; Sertraline; Depression; Cohort Studies; Mirtazapine; Amitriptyline; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Cardiovascular Diseases; Denmark
PubMed: 37849303
DOI: 10.1176/appi.ajp.20230356 -
Expert Review of Neurotherapeutics Apr 2024Gambling disorder (GD) is a mental health condition characterized by persistent and problematic betting behavior. GD generates distress and impairment, and treatment... (Review)
Review
INTRODUCTION
Gambling disorder (GD) is a mental health condition characterized by persistent and problematic betting behavior. GD generates distress and impairment, and treatment options include psychological and pharmacological interventions.
AREAS COVERED
This narrative review explores existing pharmacological treatments for GD. The following classes of medications were considered: opioid-receptor antagonists (e.g. naltrexone and nalmefene), serotonin reuptake inhibitors (e.g. fluvoxamine, paroxetine, sertraline, escitalopram, and citalopram), glutamatergic agents (e.g. N-acetylcysteine (NAC), acamprosate, and memantine), mood stabilizers (e.g. topiramate, carbamazepine, lithium), and other medications (e.g. modafinil, nefazodone, olanzapine, haloperidol, tolcapone, and bupropion).
EXPERT OPINION
Due to the limitations of the studies reviewed, solid conclusions regarding the optimal choice of pharmacotherapy for individuals with GD are challenging to draw at this time. Despite some medications, such as naltrexone and nalmefene, showing promising results, efficacy has varied across studies. The review highlights current gaps/limitations, including small sample sizes, limited diversity in participant demographics, the need for exploring different gambling subtypes and treatment responses, high placebo response rates, lack of longer-term longitudinal information, limited investigation of neurobiological correlates and co-occurring disorders, and the importance of implementation research. Further research is needed to address these gaps and explore additional medications, as well as interventions like neuromodulation.
Topics: Humans; Gambling; Naltrexone; Behavior, Addictive; Narcotic Antagonists; Selective Serotonin Reuptake Inhibitors
PubMed: 38357896
DOI: 10.1080/14737175.2024.2316833 -
American Family Physician Sep 2023Peripartum depression is one of the most common disorders of pregnancy. It has a higher morbidity and mortality risk than any other condition affecting pregnant people....
Peripartum depression is one of the most common disorders of pregnancy. It has a higher morbidity and mortality risk than any other condition affecting pregnant people. The American Academy of Family Physicians, the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the U.S. Preventive Services Task Force recommend that pregnant patients be screened for depression with one of several validated tools and offered treatment with psychotherapy and medication. There are no validated tools available to identify who is at increased risk of peripartum depression. Risk factors for peripartum depression include a history of depression, a history of physical or sexual abuse, carrying an unplanned or unwanted pregnancy, and traumatic birth. The U.S. Preventive Services Task Force recommends offering psychotherapy to patients at increased risk of depression because it can decrease the development of peripartum depression by up to 39%. Untreated peripartum depression increases the risk of adverse pregnancy outcomes and mortality for the patient, as well as negative outcomes for the newborn, including growth faltering, developmental delay, and attachment disorder. Cognitive behavior therapy and interpersonal psychotherapy are the mainstay of treatment for peripartum depression; physicians should consider selective serotonin reuptake inhibitors for those with moderate to severe depression. The benefits of selective serotonin reuptake inhibitors generally outweigh the risks; however, fluoxetine and paroxetine should be avoided during pregnancy because they can cause an increased risk of birth defects.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Child; Selective Serotonin Reuptake Inhibitors; Depression; Peripartum Period; Psychotherapy; Advisory Committees
PubMed: 37725459
DOI: No ID Found -
Expert Review of Neurotherapeutics 2023Recommendations for treating panic disorder (PD) in older patients are scarce. The authors have systematically reviewed whether several recommended medications are... (Review)
Review
INTRODUCTION
Recommendations for treating panic disorder (PD) in older patients are scarce. The authors have systematically reviewed whether several recommended medications are superior to others and their optimal doses in this age group.
METHODS
A database search of studies involving patients with PD with/without agoraphobia aged ≥ 60 years was carried out using PubMed, PsycINFO, Embase, and Clinical Trials.gov, from their inception dates to 1 March 2023. Only four (published from 2002 to 2010) of the 1292 records screened were included. A risk of bias assessment was provided. This systematic review was performed using The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).
RESULTS
Two studies were randomized clinical trials, whereas two were open-label, including paroxetine, citalopram, escitalopram, and sertraline; three studies reported short-term evaluations, whereas one study included a 26-week follow-up. Medications provided benefits, with good tolerability. Preliminary results suggested greater benefits of paroxetine in reducing panic attacks vs. cognitive - behavioral therapy, and an earlier decrease in PAs with escitalopram vs. citalopram. Risk of bias was considerable.
CONCLUSIONS
The pharmacological management of PD in older patients has received no attention. Findings are scant, dated, and affected by methodological flaws; thus, they do not provide significant advances.
Topics: Humans; Aged; Panic Disorder; Paroxetine; Citalopram; Selective Serotonin Reuptake Inhibitors; Escitalopram; Randomized Controlled Trials as Topic
PubMed: 37676054
DOI: 10.1080/14737175.2023.2254938