Modafinil

The meta-analysis was conducted and reported according to recommendations of the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group [36] (link). A review protocol was construed following the MOOSE guidelines. This was not published but only for internal use of this study.
A PubMed and Embase search was conducted for articles on metabolic side effect profiles of antipsychotic medication. The search term used was: ((“weight gain” OR “BMI” OR “7% weight”) AND (chlorpromazine OR haloperidol OR bromperidol OR fluphenazine OR zuclopenthixol OR pentixol OR flupentixol OR levopromazine OR perphenazine OR pimozide OR penfluridol OR sulpiride OR amisulpride OR amoxapine OR asenapine OR aripiprazole OR blonanserine OR clozapine OR iloperidone OR melperone OR olanzapine OR risperidone OR paliperidone OR quetiapine OR sertindole OR lurasidone OR ziprasidone)) NOT (addition OR additive OR adjunctive OR augmentation OR lithium OR valproate OR carbamazepine OR metformin OR topiramate OR ramelteon OR rimonabant OR modafinil OR sibutramine OR genetics OR pharmacokinetics OR vomiting OR nausea OR review OR “cognitive behavioural therapy” OR “cognitive behavioral therapy” OR delirium OR steroids OR ropinirole OR sleep OR “brain volume”)
Limits Activated: Humans, Clinical Trial, Randomized Controlled Trial, Clinical Trial, Phase IV, Controlled Clinical Trial, English, German, All Adult: 18+ years, Publication Date from 1999/01/01 to 2011/12/31.

The data for this study resulted from a survey conducted in 2011 among 3,306 German-speaking surgeons who attended five international conferences of the German Society of Surgery (Deutsche Gesellschaft für Chirurgie). After the first conference, potential participants were asked if they had been assessed before; those who had been were excluded from a second participation.
Based on previous research about prescription and illicit drugs for CE, an AQ about the use of prescription and illicit drugs for enhancing cognitive functions or mood was developed and distributed to the participants during the conferences. The AQ asked about the ‘non-medical use of stimulants with the particular intention of CE’ and ‘the non-medical use of antidepressants with the particular intention of ME’ during lifetime, last year, last month and last week (frequency). Furthermore, we asked for the age of first use. Beyond that, the AQ included questions about potential risk factors associated with usage of drugs and questions about biometrical parameters (for example, gender, age, age of first use, and so on.). We were mainly interested in healthy participants using drugs specifically for CE or ME. Therefore, the data of participants with self-reported psychiatric disorders (for example, depression, attention deficit/hyperactivity disorder, (ADHD)) who had physicians’ prescriptions for any drug were excluded.
Participants were asked to drop the questionnaire into black boxes after having filled in the questionnaire anonymously.
The study was carried out according to the Principles for Medical Research Involving Human Subjects according to the Declaration of Helsinki. The study was approved by the local Ethics Committee (Landesärztekammer Rheinland-Pfalz) (No. 837.321.08 (6318)). Participants gave informed consent by returning the questionnaire and were informed about this procedure in the introduction section of the questionnaire; this procedure was approved by the above mentioned local Ethics Committee.
The AQ contained questions about the use of drugs for CE and ME as well as questions using RRT. After a brief introduction about the RRT stressing the anonymity of this technique, questions were presented to participants as follows:
Please consider a certain birthday (yours, your mother’s, etc.). Is this birthday in the first third of a month (1st to 10th day)?
If yes, please proceed to Question A; if no, please proceed to Question B.
Question A: Is this birthday in the first half of the year (prior to the first of July)?
Question B: Did you ever use prescription and/or illicit drugs (e.g. Methylphenidate, Modafinil, illicit Amphetamines, and so on) without a medical need for cognitive enhancement?
Note that only you know which of the two questions you will answer
o Yes o No
For assessing the use of antidepressants for mood enhancement, we modified Question B as follows: ‘Did you ever use antidepressants without medical need for enhancing your mood and/or self-esteem, self-presentation?’
The interviewers are not able to know which question the respondent has to answer. Therefore, participants can reply honestly without compromising themselves. Of all participants, 67.1% (245.25/365.25) received the sensitive question (B) and 32.9% (120/365.25) the non-sensitive question (A).
${\widehat{\pi }}_s=\frac{a-\left(1-p\right){\pi }_N}{p}$
the proportion of ‘yes’ responses with respect to the sensitive questions can be estimated from proportion a of total ‘yes’ responses in the sample. p denotes the probability of receiving the sensitive question (Question B; p = 67.1% of all participants received this question). The probability of answering the non-sensitive question (A) with ‘yes’ is π_n = 49.6% (181.25/365.25). A 95% confidence interval (CI) for the unknown prevalence can be computed from the sampling variance
$\mathit{Var}\left({\widehat{\pi }}_s\right)=\frac{a\left(1-a\right)}{n{p}^2}$
where n denotes the sample size [33 (link),39 (link)].
$\begin{array}{l}\begin{array}{l}\mathrm{For}\mathrm{example}\mathrm{for}\mathrm{a}=328/1105\approx 0.30,\\ \mathrm{p}=245.25/365.25\approx 0.67,\\ {\mathrm{\pi }}_{\mathrm{N}}=181.25/356.25\approx 0.50,\mathrm{and}\\ \mathrm{n}=1105,\mathrm{this}\mathrm{yields}\end{array}\hfill \\ {\widehat{\mathrm{\pi }}}_{\mathrm{s}}=\frac{328/1105-\left(1-245.25/365.25\right)181.25/365.25}{245.25/365.25}\hfill \\ \approx 0.1993=19.93\%.\\ {\mathrm{Var}(\widehat{\mathrm{\pi }}}_{\mathrm{s}})=\frac{328/1105\left(1-328/1105\right)}{1105{\left(245.25/365.25\right)}^2}\approx 0.000419.\hfill \\ {\mathrm{SE}(\widehat{\mathrm{\pi }}}_{\mathrm{s}})=\sqrt{0.000419}\approx 0.0205=2.05\%.\hfill \\ \hfill \begin{array}{l}\mathrm{Thus}\mathrm{the}95\%\mathrm{confidence}\mathrm{interval}\mathrm{is}19.93\pm 1.962.05,\mathrm{that}\mathrm{is},\mathrm{ranges}\mathrm{from}\\ 15.91\%\mathrm{to}23.95\%.\end{array}\hfill \end{array}$
Statistical analyses were performed with SPSS for Windows, Version 17.0. Means are given with their corresponding standard deviation (SD) (mean ± SE) and Clopper-Pearson confidence intervals (95% CI). AQ questions were analyzed using a multiple logistic regression analysis. For the regression, the variable selection procedure was performed by using stepwise forward selection with a selection level of 0.05. The variables which were analyzed as potential multivariable predictors of the use of prescription or illicit drugs for CE before forward selection were (available parameters): pressure to perform at work, pressure in private life, gross income, gender, age, family status, living with children, type of employer, employment status, hours of work, satisfaction with professional success, evaluation of career opportunities, pressure to perform subjectively evaluated as burdensome and pressure to perform subjectively evaluated as harmful to health. Ordinal variables with five or more categories (pressure to perform at work, pressure in private life, gross income, pressure to perform subjectively evaluated as burdensome and pressure to perform subjectively evaluated as harmful to health) were treated as continuous variables. Table 1 shows the variables included for the regression after forward selection; all variables which significantly influence the drug use for CE/ ME are listed in this table. There are no further variables for which we adjust. The results are presented as odds ratio (ORs) with confidence limits and P-values. The regression has been analyzed by referring to cases without missing values (complete case analysis).

We searched PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, ERIC, MEDLINE, PsycINFO, OpenGrey, Web of Science Core Collection, ProQuest Dissertations and Theses (UK and Ireland), ProQuest Dissertations and Theses (abstracts and international), and the WHO International Trials Registry Platform, including ClinicalTrials.gov, from the date of database inception to April 7, 2017, with no language restrictions. We used the search terms “adhd” OR “hkd” OR “addh” OR “hyperkine*” OR “attention deficit*” OR “hyper-activ*” OR “hyperactiv*” OR “overactive” OR “inattentive” OR “impulsiv*” combined with a list of ADHD medications (appendix pp 3–15). The US Food and Drug Administration (FDA), European Medicines Agency (EMA), and relevant drug manufacturers' websites, and references of previous systematic reviews and guidelines, were hand-searched for additional information. We also contacted study authors and drug manufacturers to gather unpublished information and data (appendix p 15).
We included double-blind randomised controlled trials (parallel group, crossover, or cluster), of at least 1 week's duration, that enrolled children (aged ≥5 years and <12 years), adolescents (aged ≥12 years and <18 years), or adults (≥18 years) with a primary diagnosis of ADHD according to DSM-III, DSM III-R, DSM-IV(TR), DSM-5, ICD-9, or ICD-10. We did not restrict our search by ADHD subtype or presentation, gender, intelligence quotient (IQ), socioeconomic status, or comorbidities (except for those needing concomitant pharmacotherapy). We included studies if they assessed any of the following medications, as oral monotherapy, compared with each other or with placebo: amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methyl-phenidate (including dexmethylphenidate), and modafinil. We excluded studies with enrichment designs (eg, trials selecting drug responders only after a run-in phase), because these types of trial can potentially inflate efficacy and tolerability estimates. Full inclusion and exclusion criteria are in the appendix (pp 16, 17).
Our study protocol was registered with PROSPERO (number CRD42014008976) and published.³⁰ We followed the PRISMA extension for network meta-analyses.³¹ (link)

Propane-2-ol (PrOH, for HPLC, ≥99.9%), acetonitrile (ACN, gradient grade, for HPLC, ≥99.9%), diethylamine (DEA, ≥99.5%), 2-propylamine (IPA, ≥99.5%), triethylamine (TEA, ≥99%), trifluoroacetic acid (TFA, 99%), and acetic acid (ReagentPlus^® > 99%) were supplied by Sigma–Aldrich (St. Louis, MO, USA). Methanol (MeOH, supergradient grade, for HPLC, ≥99.9%) and ethanol absolute (EtOH, gradient grade, for HPLC, >99.7%) were purchased from VWR International (Radnor, PA, USA). Water (Chromasolv Plus, for HPLC) was obtained from Honeywell (Charlotte, NC, USA). Pressurized liquid CO₂ 4.5 grade (99.995%) was purchased from Messer (Prague, Czech Republic). Chiral compounds: pyrovalerone, cathinone, ketamine, and amphetamine derivatives were purchased from internet vendors and tested for identity prior to use. Modafinil was purchased from Carbosynth Ltd. (Compton, United Kingdom). Chlorthalidone, citalopram, and praziquantel were supplied by Sigma–Aldrich (St. Louis, MO, USA). The list of compounds used in this work with their structures is given in Table S1 in the Supplementary Material.

New admissions were screened for MS and eligibility criteria were evaluated in a joint effort by the treating neuropsychologists (JN, JS, EH) and the principal investigator (FW). Inclusion criteria were a relapsing-remitting or secondary-progressive disease course (2017 McDonald criteria [21 (link), 22 (link)]), age between 18 and 67 years (age for retirement in Germany), Expanded Disability Status Scale (EDSS) ≤ 5.0 [23 (link)], Fatigue Scale for Motor and Cognitive Functions (FSMC) ≥ 53 (cut-off for ‘moderate fatigue’) [24 (link)], and written informed consent. Exclusion criteria included the inability to attend aquatic therapy, comorbidities, that prevented attending study sessions, chronic neurologic conditions other than MS, insufficient German language skills, and specific fatigue medication (Amantadine, Modafinil) started less than 3 months ago. If deemed eligible, pwMS were informed about the study verbally and in written form.