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Introduction and purpose: Major depressive disorder (MDD) is the most common psychiatric illness, affecting millions of people worldwide. The first line of pharmacological treatment is usually monoamine reuptake inhibitors. Up to 60% of cases, may be drug-resistant patients, prompting researchers to research substances other than conventional. 1 The purpose of this article was to review recent studies on the use of ketamine in the treatment of drug-resistant depression and present their findings. Brief description of the state of knowledge: Ketamine has been a well-known drug used in anesthesiology and pain management for decades. Because of its multidirectional effects, researchers have become interested in its effects on psychiatric illnesses. Over the past decade or so, there has been a definite increase in research and articles on the use of ketamine in psychiatry. The study has resulted in FDA approval of esketamine for the treatment of treatment-resistant depression in adults in 2019. Material and method: This article is the result of searching keywords on databases such as Google Scholar and Pubmed and collecting scientific literature about depression and ketamine. Articles were preselected by title, number of citations, source, and publication date. Summary: Ketamine has the potential to be a treatment for drug-resistant depression. Its effectiveness varies with the form and dosage, with racemic and higher doses offering greater therapeutic benefits. Ketamine's efficacy is on par with the electroconvulsive therapy. Its onset is faster than traditional antidepressants, significantly reducing suicide risk in a shorter time frame. While the precise mechanisms of its antidepressant effects are not fully understood, it is suggested that its impact on brain neuroplasticity may contribute to the rapid onset of action. Growing evidence supports ketamine's effectiveness in treating TRD, highlighting the need for further research in this area.

Abstract The domain of psychiatric drug development is currently witnessing a notable transformation, with a paramount emphasis on targeting nonmonoamine receptors and exploring inventive mechanisms of action. This paper presents an overview of the ongoing advancements in antipsychotic and antidepressant drug development. Historically, antipsychotics predominantly targeted dopamine receptors, but there is now an escalating interest in drugs that act on alternative receptors, exemplified by the TAAR1 receptor. One noteworthy candidate is Ulotaront (SEP‐363856), an agent acting as a TAAR1 agonist with 5‐HT1A agonist activity, demonstrating promising outcomes in the treatment of schizophrenia, devoid of extrapyramidal symptoms or metabolic side‐effects. Similarly, MIN‐101 (Roluperidone) and KarXT are currently in development, with its focus on addressing the symptoms in schizophrenia. In the domain of antidepressants, novel therapeutic approaches have surfaced, such as Auvelity, a Food and Drug Administration (FDA)‐approved NMDA receptor antagonist synergistically combined with Bupropion to enhance its effects. Another notable candidate is Zuranolone, operating as a GABA A receptor‐positive allosteric modulator, showcasing efficacy in treating major depressive disorder (MDD) and postpartum depression. Additionally, TAK‐653 (NBI‐1065845) and MJI821 (Onfasprodil) have emerged as potential antidepressants targeting AMPA receptors and NMDA receptor 2B (NR2B) negative allosteric modulation, respectively. This paper underscores the transformative potential of these novel drug candidates in psychiatric treatment and their ability to address cases that were previously treatment‐resistant. By focusing on nonmonoamine receptors and introducing innovative mechanisms, these drugs offer a promising prospect of improved outcomes for individuals suffering from schizophrenia and MDD. Thus, sustained attention and dedication to the development of such drugs are essential to augmenting the therapeutic options available for psychiatric patients.

Abstract Background Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. Methods STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1–2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. Discussion Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. Trial registration ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.

Warunya Woranush,1,2 Mats Leif Moskopp,2,3 Annahita Sedghi,1 Isabella Stuckart,1 Thomas Noll,2 Kristian Barlinn,1 Timo Siepmann1 1Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 2Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 3Vivantes Klinikum im Friedrichshain, Charité Academic Teaching Hospital, Klinik für Neurochirurgie, Berlin, GermanyCorrespondence: Timo SiepmannDepartment of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetschertstr. 74, Dresden, 01309, GermanyTel +49 175-613-14546Email timo.siepmann@ukdd.dePurpose: Post-stroke depression (PSD) occurs in one-third of stroke survivors, leading to a substantial decrease in quality of life as well as delayed functional and neurological recovery. Early detection of patients at risk and initiation of tailored preventive measures may reduce the medical and socioeconomic burden associated with PSD. We sought to review the current evidence on pharmacological and non-pharmacological prevention of PSD.Materials and Methods: We conducted a systematic review using PubMed/MEDLINE and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including randomized controlled studies. Eligible studies were included when performed within 1 year after the index cerebrovascular event. Animal and basic research studies, studies lacking a control group, review papers, and case reports were excluded.Results: Out of 150 studies screened, 37 met our criteria. Among the strategies identified, administration of antidepressants displayed the most robust evidence for preventing PSD, whereas non-pharmacological interventions such as psychotherapy appear to be the most frequently used approaches to prevent depression after stroke. Research suggests that the efficacy of PSD prevention increases with the duration of preventive treatment. Seven out of 11 studies (63%) that used pharmacological and eight out of 16 (50%) that used non-pharmacological interventions reported a positive preventive effect on PSD.Conclusion: Overall, the current literature on PSD prevention shows heterogeneity, substantiating a need for well-designed randomized controlled trials to test the safety and efficacy of pharmacological as well as non-pharmacological and composite prevention regimens to minimize the risk of PSD in stroke survivors. Integrative strategies combining personalized non-pharmacological interventions such as educational, mental, and physical health support, and pharmacological strategies such as SSRIs may be the most promising approach to prevent PSD.Keywords: PSD, antidepressant, depression, prevention, stroke

Background : New antidepressant strategies are needed, due to unsatisfactory clinical efficacy and many side effects of commonly used drugs. Recent studies linking the pathophysiology of depression with glutamatergic imbalance. There is hyperactivity of the main excitatory system (glutamatergic) to its inhibition (GABAergic). N-methyl D-aspartate (NMDA) receptors as a part of glutamatergic synapses are potential targets for intervention. Antagonist administration for glutamatergic systems, such as zinc, can exhibit antidepressant effects. Objective : To observe the effect of zinc administration on NMDA receptors in depressed subjects Methods : In this paper, we provide a literature review. The method to achieve the objective consists of using literature exploration, which was conducted from February to June 2022 by searching the relevant studies from several databases. Results : Study trials both in human and animal subjects reveal that depression is associated with a lower concentration of zinc. Comparison between the lowest zinc intake with the highest zinc intake had significantly lower incidence of developing depression. Dietary zinc deficiency induces depression along with upregulation of the NMDA receptor complexes. Zinc’s antidepressant effects might be mediated through its action reducing NMDA channel-opening frequency. Conclusions : The presence of zinc may downregulate the glutamate response in binding to NMDA receptors. Because of numerous studies about the connection between zinc and depression, it seems that zinc may have the potency to develop new antidepressants. Since the capability of zinc administration to reduce depressive symptoms, it is expected leading to increased medication adherence, lower costs and better outcomes.

Crocus sativus L. (C. sativus), known as “plant gold ”, has numerous functions in traditional Chinese medicine, including promoting blood circulation, removing blood stasis, cooling blood, detoxifying, relieving depression, and calming the nerves. Its stigma, the main medicinal part, performs extremely low yield and high price, thus the scarce resources, while its petals, the by-product, are usually discarded or employed as fertilizer or feed, resulting in huge waste, as the petals have been proved to contain various chemical components covering terpenoids, flavonoids, and glycosides, which exhibits pharmacological activities of analgesia, anti-inflammatory, cardiovascular protection, liver protection, and antidepressant. This paper aims to compare the material basis of the pharmacological similarities or differences between stigmas and petals, clarify their research status, and evaluate the potential application value of petals. As a by-product of a precious traditional herbal medicine, the petals of C. sativus have been elucidated in previous studies. This review explores the chemical constituents and pharmacological effect of stigma and petals of C. sativus, confirming their similar material bases, and the application prospect of petals.

Now 30 years old, the chronic mild stress (CMS) model of depression has been used in >1300 published studies, with a year-on-year increase rising to >200 papers in 2015. Data from a survey of users show that while a variety of names are in use (chronic mild/unpredictable/varied stress), these describe essentially the same procedure. This paper provides an update on the validity and reliability of the CMS model, and reviews recent data on the neurobiological basis of CMS effects and the mechanisms of antidepressant action: the volume of this research may be unique in providing a comprehensive account of antidepressant action within a single model. Also discussed is the use of CMS in drug discovery, with particular reference to hippocampal and extra-hippocampal targets. The high translational potential of the CMS model means that the neurobiological mechanisms described may be of particular relevance to human depression and mechanisms of clinical antidepressant action.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for patients with depression who have not achieved optimal outcomes with one or more trials of antidepressant medication. It is an effective antidepressant treatment but there remains considerable scope for improving clinical outcomes. One method to potentially enhance the efficacy of rTMS is through the improvement of methods of stimulation localization. Objective: The purpose of this paper is to review the literature pertaining to rTMS localization methods and approaches relevant to the treatment of major depressive disorder (MDD) and provide specific opinions on the state of the art in regards to targeting of rTMS treatment in depression. Methods: A targeted review of the literature on rTMS targeting in depression. Results: There is emerging evidence that optimal rTMS treatment outcomes are likely to be achieved with stimulation at a relatively anterior stimulation site in the left dorsolateral prefrontal cortex (DLPFC). However, some lines of research suggest that there may be two effective stimulation sites: one quite posterior, and one more anterior, in the DLPFC. The ‘Beam F3’ method provides reasonable localization to the anterior stimulation site and the posterior stimulation site corresponds to that typically used in studies using the ‘5 cm method’. Neuro-navigational methods are generally most likely to consistently ensure placement of the TMS coil such that it results in stimulation of a selected cortical site. fMRI – connectivity based approaches to targeting specific circuits in the DLPFC are intellectually attractive but it may not be possible to demonstrate differential effectiveness of these over the methods most commonly been used in clinical practice. Conclusions: There is an emerging literature helping to improve our understanding of the optimal methods for targeting rTMS treatment for depression. However, we lack substantive prospective clinical trials demonstrating improved clinical outcomes with these techniques.

Introduction The efficacy and of current antidepressants is insufficient. Esketamine, a new antidepressant administered by nasal route, is available since 2019 in the management of resistant characterized depressive episodes. Objectives To evaluate the response profile of patients to Esketamine in our institution specialized in mental health. Methods We included all patients treated with Esketamine in our institution from November 2019 to September 2021.We collected efficacy and tolerability data using the computerized and paper patient record, prescribing support software, and nursing staff. Results Since 2019, we treated 11 patients with Esketamine in combination with an antidepressant as indicated in the MA. Two patients from the 11 were found resistant, three discontinued due to adverse events, four relapsed after an initial clinical response, and two were still ongoing at the end of the study. Conclusions Despite an initial and rapid response, our study does not highlight any long-term efficacy of Esketamine in resistant depressive disorder. This highlight the fact that its use in the acute phase of depression or earlier in the management strategy could be a good alternative because of its rapid onset of action. Esketamine was initiated as a last line therapy, which may represent a bias in the evaluation of the molecule, as the later the depression is treated, the lower the response rate. The place of Esketamine in the therapeutic strategy is not yet well determined due to a lack of hindsight, and the question of pharmacological tolerance and dependence on the molecule arises. Disclosure No significant relationships.

Background: Psychiatric disorders contribute significantly to worldwide morbidity and mortality. In the case of depression and schizophrenia, effective drug therapy is available but 30-50% of patients do not respond sufficiently to the initial treatment regimen. Apart from the development of new molecules, it is desirable to optimize treatment outcomes with agents that are currently available. Therapeutic drug monitoring (TDM) is a suitable and widely accepted approach for improving the efficacy and safety of these drugs. Methods: A review of the relevant literature published between 2006 and January 2015. Results and Conclusions: This review describes major advances and drawbacks in the field of chromatography coupled with single or tandem mass spectrometry (LC-MS, LC-MS/MS and GC/MS) of selected antidepressants (agomelatine, vilazodone) and antipsychotics (iloperidone, asenapine, amisulpride, aripiprazole, melperone, zotepine, ziprasidone). The high specificity in combination with high sensitivity makes these techniques an attractive complementary method to traditional procedures used in routine practice for TDM.

Cheng Cheng,1 Jie Bai2 1School of Nursing, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Cheng Cheng, Email chengcheng@fudan.edu.cn View the original paper by Dr Cheng and colleagues This is in response to the Letter to the Editor

Ling-Ling Zhu,1 Quan Zhou2 1Geriatric VIP Ward, Division of Nursing, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang Province, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang Province, People’s Republic of ChinaCorrespondence: Quan Zhou, Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, People’s Republic of China, Tel +86-571-8778-4615, Email zhouquan142602@zju.edu.cn View the original paper by Dr Cheng and colleagues. A Response to Letter has been published for this article.

Ling-Ling Zhu,1 Quan Zhou2 1Geriatric VIP Ward, Division of Nursing, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang Province, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang Province, People’s Republic of ChinaCorrespondence: Quan Zhou, Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang Province, People’s Republic of China, Tel +86-571-8778-4615, Email zhouquan142602@zju.edu.cn View the original paper by Mr Wang and colleagues

Although antidepressant drugs appear to play an active role in increasing fracture risk, their weight is still unclear. We conducted a PRISMA compliant systematic review and meta-analysis through PubMed/Scopus/Cochrane libraries and registered with PROSPERO (registration number CRD42021254006) to investigate the relationship between antidepressant drugs categories, including SSRIs, SNRIs, and TCAs, and the risk of hip and vertebral fractures. After screening 3122 items, we finally found 26 papers for qualitative analysis and 11 for quantitative synthesis. A total of 15,209,542 adult and elderly patients were identified, with a mean follow-up of 51 months and a major prevalence of women. We identified results largely for SSRIs, with only a small amount of data for SNRIs, TCAs, and NaSSA. No data were found among the most recent categories of antidepressants, such as vortioxetine and esketamine. All included studies reported hip fractures, while three of them also included vertebral fractures. Overall, we observed a significant effect of SSRIs on fracture risk with a mean effect of 0.98 (95% CI = 0.75–1.20). This meta-analysis reveals that the use of SSRIs increases the risk of fractures. Clinicians’ awareness in antidepressant prescription should optimize their potential while reducing this risk.

The United States Food and Drug Administration issued a Black Box warning in October 2004 after placebo-controlled trials of antidepressant medications found an increased risk of suicidal thoughts and behaviors among children and adolescents taking antidepressant medications relative to placebo. Subsequently, some researchers have concluded that the Black Box warning caused severe unintended consequences; specifically, they have argued that the warning led to reduced use of antidepressants among youth, which led to more suicides. In this paper, we critically examine research regarding the Black Box warning’s alleged deleterious consequences. One study claimed that controlled trials did not actually find an increased risk of suicidality among youth taking fluoxetine relative to those taking placebo, but its measure of suicidality is likely invalid. We found that ecological time series studies claiming that decreasing antidepressant prescriptions are linked to higher rates of suicide attempts or actual suicides among youth were methodologically weak. These studies exhibited shortcomings including: selective use of time points, use of only a short-term time series, lack of performing statistical analysis, not examining level of severity/impairment among participants, inability to control confounding variables, and/or use of questionable measures of suicide attempts. Further, while some time-series studies claim that increased antidepressant prescriptions are related to fewer youth suicides, more recent data suggests that increasing antidepressant prescriptions are related to more youth suicide attempts and more completed suicides among American children and adolescents. We also note that case-control studies show increased risk of suicide attempts and suicide among youth taking antidepressants, even after controlling for some relevant confounds. As clinical trials have the greatest ability to control relevant confounds, it is important to remember such trials demonstrated increased risk of suicidality adverse events among youth taking antidepressants. The Black Box warning is firmly rooted in solid data whereas attempts to claim the warning has caused harm are based on quite weak evidence.

Paroxetine is an antidepressant included in the group of selective serotonin reuptake inhibitors (SSRI) with antidepressant and anxiolytic properties. A rarely seen adverse effect of paroxetine is dermatological reactions. Commonly seen reactions to paroxetine are eczematous reactions and benign skin lesions in general, while some clinical pictures such as life-threatening Stevens–Johnson syndrome and toxic epidermal necrolysis can also be seen. A case of a female patient who developed urticaria during paroxetine use is discussed in this paper.

The synthesis of [9, 10-dihydro-9-(4-methylaminobutyl)-9, 10-propanoanthracene] (2) as a homolog of the antidepressant [9, 10-dihydro-9-(3-methylaminopropyl)-9, 10-ethanoanthracene] (1) is described in the present paper. The key intermediate [9, 10-dihydro (4-pentyl)-9, 10- propanoanthracene-12-one] (7) is successfully synthesized by using the reaction of α-bromoacrolein with 9-pent-4-enyl-anthracene (4) followed by ring expansion and samarium diiodide deoxygenation.

Major depressive disorder is a serious mental disorder in which treatment with antidepressant medication is often associated with sexual dysfunction (SD). Given its intimate nature, treatment emergent sexual dysfunction (TESD) has a low rate of spontaneous reports by patients, and this side effect therefore remains underestimated in clinical practice and in technical data sheets for antidepressants. Moreover, the issue of TESD is rarely routinely approached by clinicians in daily praxis. TESD is a determinant for tolerability, since this dysfunction often leads to a state of patient distress (or the distress of their partner) in the sexually active population, which is one of the most frequent reasons for lack of adherence and treatment drop-outs in antidepressant use. There is a delicate balance between prescribing an effective drug that improves depressive symptomatology and also has a minimum impact on sexuality. In this paper, we detail some management strategies for TESD from a clinical perspective, ranging from prevention (carefully choosing an antidepressant with a low rate of TESD) to possible pharmacological interventions aimed at improving patients’ tolerability when TESD is present. The suggested recommendations include the following: for low sexual desire, switching to a non-serotoninergic drug, lowering the dose, or associating bupropion or aripiprazole; for unwanted orgasm delayal or anorgasmia, dose reduction, “weekend holiday”, or switching to a non-serotoninergic drug or fluvoxamine; for erectile dysfunction, switching to a non-serotoninergic drug or the addition of an antidote such as phosphodiesterase 5 inhibitors (PD5-I); and for lubrication difficulties, switching to a non-serotoninergic drug, dose reduction, or using vaginal lubricants. A psychoeducational and psychotherapeutic approach should always be considered in cases with poorly tolerated sexual dysfunction.

Bupropion is an antidepressant that is effective in the treatment of major depressive disorders, smoking cessation, and sexual side effects of selective serotonin reuptake inhibitors. Acute dystonia is characterized by prolonged muscle contraction often represented by spasms of the head and neck muscles as well as occasional jaw clenching and temporomandibular joint syndrome. Although it is believed that dystonia is the result of an abnormality of the basal ganglia, its pathophysiology is still unclear. A few cases of dystonia resulting from bupropion have been reported in prior research papers. This case report discusses a patient who had a neck spasm painful enough to wake him up and dystonic distortion after taking only one dose of 75 mg bupropion. The patient was a young 34-year-old man with a diagnosis of obsessive-compulsive disorder treated with 60 mg fluoxetine. Bupropion was added to his medications because of sexual side effects caused by the fluoxetine. It seems that we must be careful to watch for dystonic symptoms when bupropion is mixed with other drugs that affect serotonin reuptake. Although dystonia is a rare side effect of bupropion, physicians should be aware of it and manage it if it occurs.

Major depressive disorder (MDD) remains a huge personal and societal encumbrance. Particularly burdensome is a virulent subtype of MDD, treatment resistant major depression (TMRD), which afflicts 15-30% of MDD patients. There has been recent interest in N-methyl-D-aspartate (receptors (NMDARs) as targets for treatment of MDD and perhaps TMRD. To date, most pre-clinical and clinical studies have focused on ketamine, although psychotomimetic and other side effects may limit ketamine’s utility. These considerations prompted a recent promising pilot clinical trial of nitrous oxide, an NMDAR antagonist that acts through a mechanism distinct from that of ketamine, in patients with severe TRMD. In this paper, we review the clinical picture of TRMD as a subtype of MDD, the evolution of ketamine as a fast-acting antidepressant, and clinical and basic science studies supporting the possible use of nitrous oxide as a rapid antidepressant.

In environmental epidemiological investigations, information on morbidity in terms of diagnoses are usually collected from registers or self-reports in questionnaires or interviews. The presence of symptoms is also collected via questionnaires or interviews. Researchers may try to improve the validity of self-reported diagnoses by specifically asking for physician-diagnosed disease. Another way is to enquire about medication used for certain diseases or symptoms that also may be available in registers. This can be an efficient way of finding patients with diseases associated with very specific drugs, such as levodopa in the case of Parkinson’s disease (1, 2). Studies with questionnaire items about physician-diagnosed hypertension and antihypertensive medication is an example from environmental noise research (3–10). Self-reports about the use of anti­hypertensives or other pharmaceuticals may, however, suffer from information bias, for example due to patients’ misunderstanding about the classification of drugs. A paper in the present issue of the Scandinavian Journal of Work, Environment & Health (11) focuses on antidepressant, anxiolytic, and hypnotic medications and associations with noise exposure using objective data on these drugs. It could be assumed that individuals taking such medication would have more pronounced symptoms than those responding positively to questions on mood changes, anxiety, or sleep disturbances but not using any medications. Individuals may acknowledge symptoms in a questionnaire even if they are transient, while medication requires more long-lasting symptoms and is usually prescribed in response to an illness diagnosed by a doctor. Objective data on medications were also recently reported in a cohort study on occupational nose and hypertension (12). In this case, individual data on antihypertensive medications were collected from the Danish national Prescription Registry. We found, however, no reports using similar objective data on psychotrophic drugs among workers occupationally exposed to noise. Halonen et al (11) performed a cross-sectional study of the association between modeled road traffic noise at the facades of residential addresses and questionnaire data on self-rated health and register data on certain prescribed drugs (antidepressants, anxiolytics, hypnotics) in a Finnish cohort of 15 000 people from three cities. Road traffic noise was expressed in L_den, a measure in which noise in the evening and night is weighted more than noise exposure during the day. Information about medication was collected at the individual level. Such objective data should be more valid than self-reported information on medication obtained from questionnaires. The authors found no association between modeled road traffic noise and prescribed medications. They did find an association between noise and self-rated poor health (poor+average versus good+very good) among 3 000 men but not 12 000 women. Among men, the point estimate odds ratio (OR) was 1.5 in the noise stratum >60 dB, however, this was based on a relatively small sample in this noise stratum. The authors have previously reported associations between noise and sleep disturbance in part (two of the cities, N=7 000) of the same cohort (13). Symptoms of insomnia were found to be more common among women with modeled night-time noise >55 dBA. This effect was only found among women. Relatively few studies have previously collected data on medications for psychiatric symptoms. Knipschild (14) found increased purchase (per inhabitant) of hypnotics and tranquilizers in an area with high aircraft noise levels close to the Schiphol airport, compared with a control area. There was also a higher prevalence of hypnotics and tranquilizers among patients treated by general practice physicians (15). The study design was ecological, that is the associations between noise and medications could be assessed only on area and not the individual level. A few other studies have examined associations between traffic noise and psychotropic medication at the individual level, but have relied on self-reported data on medications. De Kluizenaar (8) found no association between road traffic noise and medications (sleeping pills or tranquilizers). Franssen et al (4) found a non-significant association (OR 1.25 per increase of L_den with 10 dBA) between aircraft noise around Schiphol and prescribed medication. However, there was a significantly increased OR of 2.3 (per 10 dB L_den) for non-prescribed medications, but these are less likely to be a marker for confirmed disease. Lercher et al (9) found a significantly increased OR of 1.53 between railway noise (65–75 dBA, Lden) and sleep medication in a phone interview in an Alpine valley study. Floud et al (2011) showed a significantly increased association (OR 1.28 per 10 dB increase) between aircraft noise and self-reported use of anxiolytics in seven European airports in the HYENA (HYpertension and Exposure to Noise near Airports) study (10). One additional issue that may complicate these studies of psychotropic medications is that, as well as hypnotics, anxiolytics and antidepressants may also be prescribed for sleep problems. The only previous study using data on the individual level, studied the association between road traffic noise and use of anxiolytics or hypnotics in Marseille, France (16). Among 181 000 individuals, there was no overall association, but a weak and significant association (OR 1.16) when comparing night-time noise levels >55 dBA in the least socioeconomically deprived areas. No such association was found in the more deprived areas. The authors speculate that the calculation of noise levels has less misclassification in less deprived areas with a large fraction of single-family houses compared with areas including many multi-apartment houses. Possibly also in more deprived areas, there are more socioeconomically-linked confounding factors that may obscure the association of noise exposure with anxiolytics and hypnotics. In summary, two studies with objective data on the individual level (11, 16) and one study relying on self-reports (8) showed no overall associations between road traffic noise and antidepressants, anxiolytics or hypnotics. Three studies of aircraft noise showed positive associations between noise and medications, but, in two of the studies, data on medications were self-reported (4, 10), and the one using objective data had an ecological design (14, 15). Regarding hypertension, both objective data (14, 15) and self-reports (3–8, 10) have been used. The additional value of obtaining objective data on use of medications may be larger for psychiatric symptoms than for hypertension, as the latter condition is diagnosed by a physician, and if physician-diagnosed hypertension is requested, the additional information from use of medication is probably limited. Future research should study the effects of traffic noise on psychotropic medication using data collected through registers and also link medication data in relation to noise exposure to psychiatric diagnoses and outpatient and inpatient hospital attendance data.

OBJECTIVES: Previous Danish studies have shown that employees who “work with people” (ie, do person-related work) are at increased risk of hospitalization with a diagnosis of depression. However, these studies were purely register-based and consequently unable to point to factors underlying this elevated risk. This paper examines whether person-related work is associated with incident use of antidepressants, and whether this association is mediated by several work environment exposures. METHODS: Self-reported data from the Danish work environment cohort study in 2000 were linked with the use of antidepressants between 2001–2006. We included 4958 respondents in our study after excluding those with severe depressive symptoms or use of antidepressants at baseline. RESULTS: Compared to employees doing non-person-related work, the use of antidepressants was increased statistically significantly for healthcare workers and statistically non-significantly for educational workers. The use of antidepressants was not elevated for social or customer service workers, or those doing “other” types of person-related work. The increased risks of antidepressant-use for healthcare and educational workers were attenuated when adjusted for emotional demands at work. CONCLUSIONS: The results imply that healthcare and educational workers in Denmark are at increased risk of depression and that this risk is partly mediated by the high emotional demands of the work.

Depression is a heterogeneous disorder often manifested with symptoms at the psychological, behavioral and physiological levels. Full remission is achieved in fewer than 50% of patients. Therefore, antidepressant or medications that achieve a better rate of success are urgently needed. Herbal medicine has a long and respected history, and holds a valuable place in the treatment of depression. According to medical studies, saffron can be used to treat depression. This paper reviews the clinical studied regarding the antidepressant effect of saffron