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This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Psilocybin is a tryptamine alkaloid found in some mushrooms, especially those of the genus Psilocybe. Psilocybin has four metabolites including the pharmacologically active primary metabolite psilocin, which readily enters the systemic circulation. The psychoactive effects of psilocin are believed to arise due to the partial agonist effects at the 5HT2A receptor. Psilocin also binds to various other receptor subtypes although the actions of psilocin at other receptors are not fully explored. Psilocybin administered at doses sufficient to cause hallucinogenic experiences has been trialed for addictive disorders, anxiety and depression. This review investigates studies of psilocybin and psilocin and assesses the potential for use of psilocybin and a treatment agent in neuropsychiatry. The potential for harm is also assessed, which may limit the use of psilocybin as a pharmacotherapy. Careful evaluation of the number needed to harm vs the number needed to treat will ultimately justify the potential clinical use of psilocybin. This field needs a responsible pathway forward.
Shade coffee is a well-studied cultivation strategy that creates habitat for tropical birds while also maintaining agricultural yield. Although there is a general consensus that shade coffee is more “bird-friendly” than a sun coffee monoculture, little work has investigated the effects of specific shade tree species on insectivorous bird diversity. This study involved avian foraging observations, mist-netting data, temperature loggers, and arthropod sampling to investigate bottom-up effects of two shade tree taxa - native Cordia sp. and introduced Grevillea robusta - on insectivorous bird communities in central Kenya. Results indicate that foliage-dwelling arthropod abundance, and the richness and overall abundance of foraging birds were all higher on Cordia than on Grevillea. Furthermore, multivariate analyses of the bird community indicate a significant difference in community composition between the canopies of the two tree species, though the communities of birds using the coffee understorey under these shade trees were similar. In addition, both shade trees buffered temperatures in coffee, and temperatures under Cordia were marginally cooler than under Grevillea. These results suggest that native Cordia trees on East African shade coffee farms may be better at mitigating habitat loss and attracting insectivorous birds that could promote ecosystem services. Identifying differences in prey abundance and preferences in bird foraging behaviour not only fills basic gaps in our understanding of the ecology of East African coffee farms, it also aids in developing region-specific information to optimize functional diversity, ecosystem services, and the conservation of birds in agricultural landscapes.
This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.
Many mental disorders, including depression, bipolar disorder and schizophrenia, are associated with poor dietary quality and nutrient intake. There is, however, a deficit of research looking at the relationship between obsessive–compulsive disorder (OCD) severity, nutrient intake and dietary quality.
This study aims to explore the relationship between OCD severity, nutrient intake and dietary quality.
A post hoc regression analysis was conducted with data combined from two separate clinical trials that included 85 adults with diagnosed OCD, using the Structured Clinical Interview for DSM-5. Nutrient intakes were calculated from the Dietary Questionnaire for Epidemiological Studies version 3.2, and dietary quality was scored with the Healthy Eating Index for Australian Adults – 2013.
Nutrient intake in the sample largely aligned with Australian dietary guidelines. Linear regression models adjusted for gender, age and total energy intake showed no significant associations between OCD severity, nutrient intake and dietary quality (all P > 0.05). However, OCD severity was inversely associated with caffeine (β = −15.50, 95% CI −28.88 to −2.11, P = 0.024) and magnesium (β = −6.63, 95% CI −12.72 to −0.53, P = 0.034) intake after adjusting for OCD treatment resistance.
This study showed OCD severity had little effect on nutrient intake and dietary quality. Dietary quality scores were higher than prior studies with healthy samples, but limitations must be noted regarding comparability. Future studies employing larger sample sizes, control groups and more accurate dietary intake measures will further elucidate the relationship between nutrient intake and dietary quality in patients with OCD.
One of the basic goals of second language (L2) speech research is to understand the perception-production link, or the relationship between L2 speech perception and L2 speech production. Although many studies have examined the link, they have done so with strikingly different conceptual foci and methods. Even studies that appear to use similar perception and production tasks often present nontrivial differences in task characteristics and implementation. This conceptual and methodological variation makes meaningful synthesis of perception-production findings difficult, and it also complicates the process of developing new perception-production models that specifically address how the link changes throughout L2 learning. In this study, we scrutinize theoretical and methodological issues in perception-production research and offer recommendations for advancing theory and practice in this domain. We focus on L2 sound learning because most work in the area has focused on segmental contrasts.
Obsessive–compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach.
To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5′ phosphate, and selenium.
A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive–Compulsive Scale (YBOCS), administered every 4 weeks.
An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of −7.13 (95% confidence interval = −9.24, −5.01), with a mean reduction of −1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered “responders” (YBOCS ≥35% reduction and “very much” or “much improved” on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD.
While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.
The bulk of the work on non-native speech has focused on average differences between L1 and L2 speakers. However, there is growing evidence that variability also plays an important role in distinguishing L1 from L2 speech. While some studies have demonstrated greater variability for non-native than native speech (e.g., Baese-Berk & Morrill, 2015; Wade et al., 2007), others have demonstrated that under some circumstances non-native speech maybe less variable and that variability in non-native speech may shift as a function of many factors, including task (Baese-Berk & Morrill, to appear; Baese-Berk, Morrill, & Bradlow, 2016) and L1-L2 pairing (Vaughn, Baese-Berk, & Idemaru, to appear). In the present study, we ask how variability manifests in L1 and L2 speech by speakers from a variety of language backgrounds. Specifically, we ask whether a speaker whose L1 speaking rate is highly variable is also highly variable in their L2. We also ask whether variability in speaking rate in L1 or L2 differs as a function of task (e.g., read vs. spontaneous speech) and complexity of the task (e.g., more or less complicated reading passages). The results of this study will inform our understanding of the myriad complex factors that influence non-native speech.
The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS).
This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers.
In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023).
Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.
Little is known about the early phases of bipolar disorders (BPAD) and most of current knowledge derives from putative “high-risk” studies conducted in populations of bipolar off-spring; such information may therefore be relevant only to a subgroup of at-risk subjects.
Retrospective assessment of the phase preceding the emergence of mania and of premorbid characteristics of patients treated for a first episode of psychotic mania. The collected data was used mainly to generate hypotheses.
Before onset of a first episode of psychotic mania, patients go through a phase of change from previous mental state where they present mood symptoms, sleep disruption and general functional decline. These clinical manifestations are likely to have low specificity. However, their occurrence in patients presenting certain risk factors or markers of vulnerability that were identified at a relatively high prevalence in our sample, may be an indicator of impending first episode mania.
This is a retrospective study, in a small sample of patients presenting with psychotic mania. Criteria identified need therefore to be validated in larger prospective studies.
Early identification of patients at risk to develop a first episode of psychotic mania is unlikely to be possible on the basis of symptoms alone. However, the occurrence of certain clinical characteristics in patients who have risk factors or markers of vulnerability to BPAD may be a sign of impending first episode mania.
We have developed ultra-high risk criteria for bipolar affective disorder (bipolar at-risk - BAR) which include general criteria such as being in the peak age range of the onset of the disorder and a combination of specific criteria including sub-threshold mania, depressive symptoms, cyclothymic features and genetic risk. In the current study, the predictive and discriminant validity of these criteria were tested in help seeking adolescents and young adults.
This medical file-audit study was conducted at ORYGEN Youth Health (OYH), a public mental health program for young people aged between 15 and 24 years and living in metropolitan Melbourne, Australia. BAR criteria were applied to the intake assessments of all non-psychotic patients who were being treated in OYH on 31 January.08. All entries were then checked for conversion criteria. Hypomania/mania related additions or alterations to existing treatments or initiation of new treatment by the treating psychiatrist served as conversion criteria to mania.
The BAR criteria were applied to 173 intake assessments. Of these, 22 patients (12.7%) met BAR criteria. The follow-up period of the sample was 265.5 days on average (SD 214.7). There were significantly more cases in the BAR group (22.7%, n = 5) than in the non-BAR group (0.7%, n = 1) who met conversion criteria (p < .001).
These findings support the notion that people who develop a first episode of mania can be identified during the prodromal phase. The proposed criteria need further evaluation in prospective clinical trials.
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
Pharmacokinetically important polymorphisms could guide dosing, ensuring adequate CNS bioavailability in a particular individual during a therapeutic trial. Hepatic enzyme (CYP450) polymorphisms have been extensively studied. Less work has been done on the permeability glycoprotein (P-gp) - the key efflux pump at the blood brain barrier (BBB).
An eight week prospective multi-centre candidate gene association study of 113 patients with psychiatrist diagnosed DSM-IV MDD was conducted. Subjects were treated with escitalopram (ESCIT) or venlafaxine (VEN) in a naturalistic clinical setting. Treatment outcome was assessed with the 17-item HDRS and Clinical Global Impression (CGI) Scales. Side effects were rated with a comprehensive adverse reactions scale (UKU). All response ratings were blinded to genotype. P-gp, CYP2D6, and CYP2C19 polymorphisms were assayed using microarray methodology.
BBB (P-gp) polymorphisms associated with less antidepressant CNS entry were associated with need for higher medication dosage and less overall clinical improvement. Patients with higher BBB block polymorphism need 1.45 (p = 0.018) times the dose of escitalopram than those with lower blood brain barrier block polymorphism. Patients with lower BBB block genotype had a 1.602 time greater reduction in depression compared to subjects with higher block polymorphisms (p = 0.043). Subjects with lower BBB block and poorer metaboliser status at cytochrome P450 2D6 and 2C19 genotype were significantly more likely to respond on the HDRS (RR = 1.60, 95%CI 1.095–2.339, p = 0.015).
This is the first study to demonstrated that P-gp polymorphisms predict antidepressant dose, and that combined P450 and P-gp polymorphisms predict antidepressant response.
Despite cognition being normal or even superior tocontrols prior to a first episode of mania, there is a decline in cognitivecapacity that is arguably steepest in the interval after a first episode ofmania. What is unclear, is the extent to which this can be prevented and whichagents might be most useful for doing so.
This study reports the outcomes of a single-blind, randomised control trial of maintenance therapy with lithium compared toquetiapine after a first episode of mania. Cognition and structural imagingwere the primary endpoints.
This study examined a number of paper and pencil tests ofneurocognition as well as a computerised battery including Cogstate andPresentation. Tests used include the Wechsler Test of Adult Reading, the WechslerAbbreviated Scale of Intelligence, Digit Span and Digit Symbol sub-tests of the Wechsler Adult Intelligence Scale – III, Trail Making Test, Rey Auditory VerbalLearning Test, Controlled Oral Word Association Task, Attention Network Test, Go-Nogoand Stroop Tasks. Results of this study will be presented.
Given that cognition is a major symptomatic domain ofbipolar disorder and has substantive effects on quality of life, functioningand symptomatic outcomes, the ability to influence the trajectory of cognitivechange is of considerable clinical importance.
The scales for the assessment of depressive symptoms, translated and validated in Italian, lacks in the recognition of the psychopathological nuances of the disorder. The Bipolar Depression Rating Scale (BDRS) is a tool specifically built to reflect the characteristics of bipolar depression.
- aged 18–65 years
- diagnosis of BD (DSM-IV-TR) (125 patients) or
- diagnosis of MDD (DSM-IV-TR) (30 patients)
- manifestation of depressive symptoms
- no further psychiatric comorbidity on axis I and axis II (including abuse/addiction)
The analysis of the BDRS scores, according to the Kolmogorov-Smimov method shows a normal distribution; the α Cronbach's coefficient shows that the the scale, in its Italian version, has considerable validity and reliability (r = 0.82). The factor analysis was verified using the Varimax rotational method: after several tests, we found 2 subscales, one linked to mixed/depressive symptoms and a second related to (hypo)manic symptoms.
The BDRS is a valid scale for the measurement of depression in patients with Bipolar Disorder, with a notable internal consistency (Cronbach α 0.82), a significant consistency between items/total (Cronbach α from 0.80 to 0.82) and positive correlation with other scales (MADRS r 0.67, p < 0.001; HAM-D r 0.81, p < 0.001; YMRS r 0.46 p < 0.0001), including the Young Mania Rating Scale (better than the original validation sample Berk et al., 2007).
Antidepressants are amongst the most commonly prescribed classes of drugs and their use continues to grow. Adverse outcomes are part of the landscape in prescribing medications and therefore management of safety issues need to be an integral part of practice.
We have developed consensus guidelines for safety monitoring with antidepressant treatments.
To present an overview of screening and safety considerations for pharmacotherapy of clinical depressive disorders and make recommendations for safety monitoring.
Data were sourced by a literature search using Medline and a manual search of scientific journals to identify relevant articles. Draft guidelines were prepared and serially revised in an iterative manner until all co-authors gave final approval of content.
A guidelines document was produced after approval by all 19 co-authors. The final document gives guidance on; the decision to treat, baseline screening prior to commencement of treatment, and ongoing monitoring during antidepressant treatment. The guidelines state or reference screening protocols that may detect medical causes of depression as well as screening and monitoring protocols to investigate specific adverse effects associated with antidepressant treatments that may be reduced or identified earlier by baseline screening and agent-specific monitoring after commencing treatment.
The implementation of safety monitoring guidelines for treatment of clinical depression may significantly improve outcome, by improving a patient's overall physical health status.
Bipolar disorder (BD) is a psychiatric disorder with an uncertain aetiology. Recently, special attention has been given to homocysteine (Hcy), as it has been suggested that alterations in 1-carbon metabolism might be implicated in diverse psychiatric disorders. However, there is uncertainty regarding possible alterations in peripheral Hcy levels in BD.
This study comprises a meta-analysis comparing serum and plasma Hcy levels in persons with BD and healthy controls. We conducted a systematic search for all eligible English and non-English peer-reviewed articles.
Nine cross-sectional studies were included in the meta-analyses, providing data on 1547 participants. Random-effects meta-analysis showed that serum and plasma levels of Hcy were increased in subjects with BD in either mania or euthymia when compared to healthy controls, with a large effect size in the mania group (g = 0.98, 95% CI: 0.8–1.17, P < 0.001, n = 495) and a small effect in the euthymia group (g = 0.3, 95% CI: 0.11–0.48, P = 0.002, n = 1052).
Our meta-analysis provides evidence that Hcy levels are elevated in persons with BD during mania and euthymia. Peripheral Hcy could be considered as a potential biomarker in BD, both of trait (since it is increased in euthymia), and also of state (since its increase is more accentuated in mania). Longitudinal studies are needed to clarify the relationship between bipolar disorder and Hcy, as well as the usefulness of peripheral Hcy as both a trait and state biomarker in BD.
Associations between common psychiatric disorders, psychotic disorders and physical health comorbidities are frequently investigated. The complex relationship between personality disorders (PDs) and physical health is less understood, and findings to date are varied. This study aims to investigate associations between PDs with a number of prevalent physical health conditions.
This study examined data collected from women (n = 765; ≥ 25 years) participating in a population-based study located in south-eastern Australia. Lifetime history of psychiatric disorders was assessed using the semi-structured clinical interviews (SCID-I/NP and SCID-II). The presence of physical health conditions (lifetime) were identified via a combination of self-report, medical records, medication use and clinical data. Socioeconomic status, and information regarding medication use, lifestyle behaviors, and sociodemographic information was collected via questionnaires. Logistic regression models were used to investigate associations.
After adjustment for sociodemographic variables (age, socioeconomic status) and health-related factors (body mass index, physical activity, smoking, psychotropic medication use), PDs were consistently associated with a range of physical health conditions. Novel associations were observed between Cluster A PDs and gastro-oesophageal reflux disease (GORD); Cluster B PDs with syncope and seizures, as well as arthritis; and Cluster C PDs with GORD and recurrent headaches.
PDs were associated with physical comorbidity. The current data contribute to a growing evidence base demonstrating associations between PDs and a number of physical health conditions independent of psychiatric comorbidity, sociodemographic and lifestyle factors. Longitudinal studies are now required to investigate causal pathways, as are studies determining pathological mechanisms.
Bipolar disorder (BD) is a psychiatric disorder associated with increased rates of obesity and inflammation. Leptin is an adipokine that is mainly produced by the white adipose tissue in response to insulin. It stimulates the immune system, increasing the production of pro-inflammatory cytokines. There is currently uncertainty regarding possible alterations in peripheral leptin levels across the mood states in BD.
This study comprises a between-group meta-analysis comparing serum and plasma leptin levels in people with BD in mania, depression or euthymia and healthy controls. We conducted a systematic search for all possibly eligible-English and non-English peer-reviewed articles. We calculated the effect size (ES) utilizing Hedges’ adjusted g using random effects.
Eleven studies were included in the meta-analyses, providing data on 1118 participants. Serum and plasma leptin levels were not altered in subjects with BD when compared to healthy controls in mania (g = −0.99, 95% CI −2.43 to 0.43, P = 0.171), in depression (g = 0.17, 95% CI −0.45 to 0.79, P = 0.584), or in euthymia (g = 0.03, 95% CI −0.39 to 0.46, P = 0.882). However, we did observe a stronger association between leptin levels and both age and BMI in patients with BD in euthymia compared to healthy controls, such that the greater the age of the individuals, the greater the difference in leptin levels between BD and controls; and the higher the BMI, the greater the difference in leptin levels between BD and controls.
Our meta-analysis provides evidence that leptin levels are not altered in BD across the mood spectrum compared to healthy controls. The disproportionate increase of leptin levels with increase in BMI in BD speaks in favour of a potential inflammatory role of white adipose tissue in BD and a disproportionate increase of leptin levels with increase in age.
Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania.
The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points.
There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition.
Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.