Depressive issues, like main depressive dysfunction (MDD) and dysthymia, are among the many main causes of non-fatal well being loss worldwide.1 MDD is related to vital particular person, societal and financial burden.2 Whereas pharmacological remedy with antidepressants (AD) is a well-established and efficient therapy for MDD, 30–60% of sufferers with MDD don’t reply adequately to the preliminary AD therapy3 and an estimated 40% of sufferers don’t reply to 2 consecutive AD therapies.4
Remedy-resistant melancholy (TRD) is related to a poorer high quality of life and well being standing, lower in productiveness, greater suicide danger, enhance in hospitalization charges, and better healthcare prices.5–7 A number of danger elements have been related to TRD, together with comorbidities (anxiousness and character issues), suicide danger, episode severity, episode recurrence, variety of hospitalizations, early onset, and non-response at first therapy.5,8 The reported worldwide prevalence of TRD varies broadly from 11% to 50%; this inconsistency could also be attributed to various definitions of TRD used within the totally different research and potential under-reporting of circumstances of TRD.9–13
Though many definitions for TRD have been proposed, there’s a lack of a uniformly accepted medical definition.3,14 A generally used definition of TRD is ‘failure of two consecutive ample AD trials’.3,15 A not too long ago printed Asia Pacific consensus outlined TRD as “failure of ≥2 AD therapies given at ample doses, for six–8 weeks throughout a serious depressive episode”,12 whereas a French consensus outlined TRD because the “failure of two AD of ample dose and length (optimum length of 4–6 weeks when goal dose is achieved)”.2
Within the absence of a TRD-focused therapy guideline, suggestions for the administration of TRD are sometimes included in pointers for the administration of MDD in adults.16–19 In Southeast Asia (SEA), just a few country-specific medical follow pointers present suggestions for the administration of sufferers with TRD.20–22 In these pointers, nevertheless, TRD is variably outlined and the therapy pathway for the administration of TRD varies. Moreover, SEA is a vastly numerous area, and healthcare methods (together with psychiatry) throughout SEA are extremely heterogeneous,23 rendering direct software of a world guideline to varied country-specific settings troublesome. Subsequently, there’s a want for a regional consensus that gives a uniform definition and therapy ideas that may be simply tailored to varied international locations within the SEA area to optimize the administration of sufferers with TRD. We purpose to supply consensus-based suggestions on the definition and administration of TRD in adults, which might be tailored to native contexts and carried out in medical follow by specialists in SEA.
This consensus was developed by an professional panel comprising 13 purposefully sampled nationwide psychiatrists from SEA, together with Indonesia, Malaysia, Philippines, Singapore and Thailand. All specialists work in a college or tertiary medical/psychiatric establishment, are key members in related educational or skilled associations, participated in analysis in temper issues or have intensive medical expertise in psychiatry in temper issues, and have related expertise within the administration of sufferers with TRD.
The SEA professional panel convened in November 2019 in Singapore to debate and develop a SEA-specific consensus on the definition and administration of TRD that may assist psychiatrists throughout SEA in making knowledgeable medical selections.
Previous to the consensus assembly, a thematic literature overview of TRD publications in SEA, together with the definition, administration and therapy pointers of TRD, in addition to accessible worldwide pointers of TRD was performed, and the accessible knowledge was summarized. A pre-meeting survey was then distributed to the professional panel to achieve insights on follow patterns of their respective international locations. Based mostly on the accessible proof from the literature overview and pre-meeting survey responses, a definition of TRD and 27 medical situations within the administration of TRD had been drafted for the consensus improvement (Figure 1). The thematic literature overview, pre-meeting survey and medical situations had been developed by an unbiased medical communications company (Wholesome Pondering Group Asia), following preliminary inputs from the lead creator.
Determine 1 RAND/UCLA methodology for attaining consensus.
The RAND/UCLA Appropriateness Technique was used to acquire consensus. This methodology incorporates proof from the literature in addition to professional medical opinions and has been used broadly for the event of pointers.24 The panel convened to debate the draft definition and medical situations on the consensus assembly. The panel independently and confidentially rated the appropriateness of every medical situation primarily based on a 1 to 9 Likert scale in two rounds of voting. After every spherical of voting, discrepancies within the scores had been recognized. “Disagreement” was outlined as one-third or extra of the panelists ranking a situation within the lowest 3 factors of the appropriateness scale (rating 1, 2 or 3) and one-third or extra of the panelists ranking the identical situation within the highest 3 factors of the appropriateness scale (rating 7, 8 or 9). Within the absence of “disagreement”, a ranking with a median rating of seven to 9 was thought-about “applicable”, 4 to six was “equivocal” and 1 to three was “not applicable”. After the primary spherical of voting, the panel mentioned their particular person views on the appropriateness of every medical situation earlier than continuing to the second and remaining spherical of voting. Following the consensus assembly, medical situations rated as “applicable” had been translated into consensus statements which had been subsequently refined by the professional panel. A therapy pathway primarily based on the “applicable” medical situations was additionally drafted.
Definition of TRD in Medical Follow
The professional panel deliberated on the necessity to make clear that TRD refers particularly to resistance to pharmacological remedies solely. It was agreed that “pharmacotherapy-resistant melancholy” (PRD) is a extra appropriate time period in contrast with TRD and will probably be used henceforth when referring to the consensus and opinions from the SEA professional panel.
Based mostly on the consensus, the panel agreed on the working definition of PRD in medical follow because the failure of two drug remedies of ample dose, for 4–8 weeks length with ample adherence, throughout a serious depressive episode.
Remedy Choices for PRD in Adults
Twenty medical situations within the administration of PRD in adults had been rated “applicable” (Table 1).
Desk 1 Consensus Statements on the Applicable Administration of MDD and PRD; within the Absence of Disagreement, Median Rating of seven–9 is Applicable, 4–6 is Equivocal and 1–3 is Not Applicable
4 medical situations had been rated “inappropriate” – switching therapy to a different drug throughout the similar class was thought-about as “inappropriate” in 1) an grownup affected person who has no response to 2 successive oral AD monotherapies of ample dosage, length and adherence; 2) an grownup affected person with PRD who has partial response to an AD monotherapy of ample dose, length and adherence; and three) particular conditions the place an grownup affected person is suicidal or when speedy response is required. Moreover, the usage of psychotherapy in grownup sufferers who’re suicidal or require speedy response was additionally rated as “inappropriate”.
Two medical situations had been labeled “equivocal” by the professional panel members resulting from uncertainties relating to 1) the usage of psychotherapy in an grownup affected person who has no response to 2 successive oral AD monotherapies of ample dosage, length and adherence, and a couple of) the usage of repetitive transcranial magnetic stimulation (rTMS) in particular conditions the place a affected person is suicidal or when speedy response is required.
Panel members “disagreed” on the usage of electroconvulsive remedy (ECT) in an grownup affected person with PRD who has partial response to an AD monotherapy with ample dose, length and adherence.
Remedy Pathway for MDD and PRD in Adults
The professional panel additionally proposed a simplified therapy pathway to assist the therapy of MDD in adults, together with the therapy of PRD (Figure 2).
● Step one within the proposed therapy method for MDD is to provoke an AD monotherapy with monitoring for 4–8 weeks; if required, the therapy dose might be escalated or maximized.
● In case of partial response or non-response after 4–8 weeks of therapy regardless of maximizing the therapy dose, a second AD monotherapy needs to be trialed for an extra 4–8 weeks with response monitoring; choices for second line therapy embrace switching to a unique class of ADs, augmenting or combining therapy modalities.
● Upon failure of second line of therapy following 4–8 weeks of monitoring regardless of ample dose and adherence (outlined as PRD), a third-line therapy needs to be provided; therapy choices for PRD embrace maximizing the dose, switching to a unique class, augmenting or combining therapy modalities. Mixture or augmentation therapy routine within the third line needs to be totally different from the failed routine used within the second-line therapy. Based mostly on the accessible medical knowledge and FDA approval, the panel thought-about that esketamine, an augmenting agent, might be a possible third-line possibility for the therapy of PRD.
● Non-pharmacological therapy choices might be thought-about throughout the second-line therapy of MDD, and PRD.
Determine 2 Remedy pathway to information the administration of MDD and PRD in adults within the SEA area. ^Mixture or augmentation therapy routine within the third line needs to be totally different from the failed mixture or augmentation routine utilized in second-line therapy. †Esketamine contraindications primarily based on FDA approval: aneurysm; vascular illness; recognized historical past of atrial cerebral hemorrhage; recognized historical past of hypersensitivity to esketamine, ketamine or any of the excipients; earlier ketamine abuse, bipolar dysfunction. Use with warning in uncontrolled hypertension.
Re-assessment of therapy response throughout therapy is important to optimize administration. A shorter follow-up schedule after therapy initiation is beneficial for particular populations, corresponding to sufferers with recurrent episodes, sufferers with extreme melancholy, sufferers with bodily or psychiatric comorbidities (eg, character dysfunction, twin prognosis, anxiousness dysfunction, and so on.), aged sufferers, sufferers who’re pregnant, or sufferers in danger for substance abuse. Remedy response needs to be assessed and subsequent steps determined by the clinician after cautious consideration of dangers and advantages. Medical scales (eg, CGI scale, PHQ-9) present clinicians with further assist when assessing therapy response.
Though all kinds of pharmacological therapies are at the moment accessible for the administration of MDD, many sufferers don’t present enchancment with ample doses of ADs given for ample durations, resulting in TRD. Nonetheless, there was no common definition of TRD regardless of the abundance of literature on TRD. Certainly, a scientific overview recognized 155 definitions for TRD within the literature.25 These variations within the definition renders proof synthesis and translation of analysis findings into every day medical follow difficult.14 It might additionally have an effect on the design of medical trials or observational research whose outcomes are essential for enhancing TRD therapy.14
To ascertain a uniform definition and administration ideas for sufferers with TRD in SEA, the professional panel employed the RAND/UCLA Appropriateness Technique to realize consensus. This methodology has been broadly used for the event of pointers involving medical and surgical procedures,24 however its use in a psychiatric setting is restricted. Just lately, the French Affiliation for Organic Psychiatry and Neuropsychopharmacology and the muse FondaMental printed medical pointers for the administration of TRD using the RAND/UCLA Appropriateness methodology.2 In contrast with the Delphi consensus methodology, the authors thought-about this methodology able to detecting settlement with out attempting to advertise consensus, whereas additionally probably minimizing variations between medical opinions.2
Constructing upon the generally used definition of TRD, the professional panel has developed a standard working definition for TRD that may probably be utilized in medical follow throughout the SEA area – the failure of two drug remedies of ample dose, for 4–8 weeks length, with ample adherence, throughout a serious depressive episode. Importantly, as TRD refers to failure of two drug remedies, the time period PRD could higher replicate this definition by specifying the failure to pharmacological brokers solely. Just lately printed consensus/medical pointers have beneficial a therapy length of both 4–6 weeks or 6–8 weeks as ample for outlining TRD,2,12 whereas the professional panel contemplate 4–8 weeks as a extra applicable length. The medical experiences from SEA recommend that therapy response or lack thereof often turns into obvious in 4 weeks of therapy, and it could be inappropriate to attend for six weeks in these sufferers.
Approaches to pharmacological administration of TRD embrace 1) growing or maximizing the AD dose, 2) switching to a different AD (throughout the similar class or from a unique class), 3) combining two ADs, 4) augmenting ADs with different brokers, and 5) utilizing non-pharmacological remedies (psychotherapy, mind stimulation).3 Nonetheless, therapy outcomes for TRD rely on numerous elements, together with medical options (eg, length of episode, time to AD response), psychosocial parts (eg, age, age at first therapy, length of sickness, suicidality, schooling stage), environmental stress and hectic life occasions (eg, childhood maltreatment, job loss, psychological trauma, lack of a liked one), and psychiatric (eg, anxiousness, social phobia, post-traumatic stress dysfunction) and bodily comorbidities (eg, heart problems, diabetes); and genetic elements.26
Dose escalation has been a regular follow and could also be a helpful preliminary technique for sufferers with MDD with partial response, however proof additionally means that the good thing about growing therapy dose is determined by the category of AD. For instance, tricyclic antidepressants have a longtime sturdy relationship between dose and medical response, however this isn’t true for selective serotonin reuptake inhibitors.27 When dose escalation fails, switching ADs throughout the similar class or to a unique class is often employed. A number of opinions have reported comparable outcomes between switching AD throughout the similar class and switching to a unique class of AD,28–30 however a meta-analysis confirmed that switching to a unique class of AD leads to vital, albeit modest, greater remission charges in contrast with switching throughout the similar class of AD.31 That is certainly beneficial in native pointers as properly22 and displays the medical experiences of the SEA professional panel – most sufferers achieve profit from switching to a different class of AD. Medication of the identical class have an analogous mechanism of motion and failure to at least one class of drug could require a change to a drug with a unique mechanism of motion involving a unique neurotransmitter pathway. Sufferers additionally could not want to take a unique AD from a similar class to which they’ve beforehand failed to reply. As such, switching to a different class of AD is an applicable subsequent technique for sufferers with TRD who failed two consecutive AD monotherapies regardless of ample dose, length and adherence. To change ADs, one among three methods might be employed – concurrent change, the place the dose of each medicines is modified concurrently; overlapping change, the place the present medicine is sustained on the unique dose whereas the dose of the second medicine is elevated to optimum stage; and sequential change, the place the dose of the present medicine is titrated downward till interruption and the brand new medicine is then launched.32 The efficacy of augmentation in managing TRD, particularly with atypical antipsychotics and lithium, are properly established, and this technique has been incessantly utilized in routine medical care.3 Proof for mixture technique (addition of no less than one other AD, often from a unique class) is restricted and has contradicting findings,33 however it’s a broadly used technique in routine medical follow.2,3 Each augmentation and mixture methods provide comparable benefits in sustaining the preliminary enhancements and producing a speedy response however carry the chance of elevated unwanted side effects resulting from drug–drug interactions;33 these unwanted side effects could also be troublesome to handle as a result of identification of the AD resulting in the unwanted side effects will not be a simple course of. Tapering down medicines together regimens may also be troublesome to realize. Sufferers already on a number of medicine for his or her comorbid medical circumstances could also be reluctant so as to add a number of extra medicines to handle their temper. Moreover, making certain therapy adherence is tougher with mixture remedy than monotherapy. With mixture remedy, sufferers could must take medicines a number of instances in a day and this will enhance the probability of sufferers forgetting to take the required doses, resulting in poor adherence and therefore outcomes. Comparative knowledge throughout these pharmacotherapy methods are scarce, due to this fact clinicians should finally decide the suitable therapy technique primarily based on particular person circumstances of the affected person, and cautious consideration of the risk-benefit steadiness.
Non-pharmacological approaches, together with mind stimulation methods and psychotherapy, can even assist the administration of TRD. The professional panel imagine that non-pharmacological approaches can be utilized at any level throughout the therapy of MDD and TRD.
ECT has demonstrated a great efficacy and security profile and is indicated for extreme main melancholy, mania, schizophrenia and catatonia, however it’s related to considerations about cognitive impairment and the knowledgeable consent course of; as such, its use has primarily been reserved for conditions the place AD is unable to adequately deal with extreme melancholy.34 Rising proof additionally suggests rTMS to be a helpful adjunctive modality with AD in treating TRD.35 A number of systematic opinions and meta-analyses have demonstrated the helpful impact of rTMS in enhancing depressive signs in sufferers with TRD, with or with out AD.36–38 Moreover, the reported opposed impact discontinuation charge of rTMS was solely 4.5% in distinction to 25.1% discontinuation charge for AD.39,40 In contrast with rTMS, ECT has been proven to be simpler within the therapy of melancholy.41–43 Nonetheless, sufferers receiving ECT could expertise extra cognitive unwanted side effects in contrast with these receiving rTMS.41 Moreover, mixture of ECT and AD might also enhance the incidence of reminiscence deterioration in contrast with ECT alone.44 Pointers have beneficial ECT as a first-line therapy for MDD in pressing and emergency conditions, corresponding to excessive danger of suicide and excessive ranges of misery;19,45 it may also be thought-about for the prevention of relapse as monotherapy or together with AD.2 According to this, the professional panel recommends the usage of ECT in sufferers with MDD who’re suicidal or require speedy response. Nonetheless, there was disagreement among the many panel members relating to the usage of ECT in sufferers with MDD with partial response to pharmacological therapy – whereas a number of the panel members contemplate ECT as an applicable adjunctive remedy for partial responders resulting from its confirmed efficacy, some contemplate it inappropriate for sufferers who’ve had a significant albeit partial response to therapy. On this case, additional optimization of pharmacological therapy is warranted primarily based on efficacy and cost-effectiveness concerns. Moreover, primarily based on the accessible proof, the professional panel recommends the usage of rTMS in partial responders and in sufferers with PRD however signifies uncertainty relating to its use in particular conditions the place a affected person is suicidal or requires speedy response. Sparse proof means that rTMS could also be helpful in lowering suicide danger,46,47 and therefore its use in sufferers with suicidal danger within the SEA is restricted. Whereas rTMS is a viable therapy possibility on this affected person inhabitants, additional real-world research are warranted to show the effectiveness of rTMS.
Psychotherapy has a slower onset of motion,48 however a latest Cochrane overview concluded that there’s moderate-quality proof displaying that psychotherapy as an adjunctive therapy to AD is helpful for enhancing response and remission charges within the quick time period for sufferers with TRD.49 There may be, nevertheless, no proof of profit for switching to a psychotherapy alone in contrast with persevering with an AD routine.49 As such, the professional panel considers the usage of psychotherapy in sufferers with MDD with partial response to pharmacological therapy as applicable. Nonetheless, psychotherapy will not be applicable for sufferers who’re suicidal or require speedy response due to the slower onset of motion of psychotherapy. Moreover, proof supporting the efficacy of psychotherapy in sufferers with suicidal danger are scarce. The SEA professional panel signifies uncertainty relating to the usage of psychotherapy in sufferers with PRD primarily based on their medical experiences – sufferers with PRD sometimes have extreme melancholy; they could not be capable of focus and take part actively within the means of psychotherapy resulting from an absence of capacity to pay attention and management their cognitive distortion. Moreover, there’s a lack of standardized certification for psychotherapy and certified psychotherapists or medical psychologists within the SEA area. Native pointers additionally don’t suggest adjunctive psychotherapy within the administration of sufferers with TRD resulting from restricted proof.22
Just lately, the US Meals and Drug Administration and the European Medicines Company permitted esketamine nasal spray, at the side of an oral AD, for TRD in adults.50,51 Esketamine is the S-enantiomer of ketamine that considerably reduces signs of melancholy in TRD with an appropriate security profile.52 Reported unwanted side effects of esketamine are sometimes gentle and transient.53,54 Moreover, esketamine has a speedy onset of motion and maintains therapy response with continued use.53,54 Nonetheless, you will need to word that there are security considerations over sedation and dissociation, and a possible for misuse and abuse of esketamine. Subsequently, it might solely be prescribed and administered by licensed healthcare suppliers in licensed facilities the place sufferers might be monitored for opposed occasions for no less than 2 hours after therapy initiation.50 Knowledge from long-term follow-up research will additional present insights on issues of safety and long-term use of esketamine. Regardless, esketamine could also be a helpful addition to the restricted therapy armamentarium of TRD. On the time of the consensus assembly, esketamine in Asia was solely permitted and accessible in South Korea.55 Nonetheless, it’s now permitted and accessible in Singapore,56 Malaysia,57 the Philippines,58 and Indonesia.59 Based mostly on the accessible medical knowledge and the FDA label, esketamine needs to be used with warning in sufferers with an elevated danger of substance use issues and all exclusions listed within the FDA approval for esketamine needs to be thought-about as exclusions for the usage of esketamine within the SEA as properly. Persona issues shouldn’t be thought-about an exclusion for the usage of esketamine; in these sufferers, the clinician’s judgement ought to information the usage of esketamine.
Our consensus on the pharmacological therapy methods for sufferers with MDD and TRD is usually according to present pointers.2,17–19 Nonetheless, our consensus doesn’t present particular suggestions on dosing and brokers, as availability and accessibility of therapy brokers fluctuate throughout the SEA area. As an alternative, we offer a therapy pathway summarizing the suitable therapy choices for the administration of sufferers with MDD and TRD (Figure 2). Our consensus on the non-pharmacological therapy methods can also be aligned with the medical pointers by Bennabi et al2 mind stimulation methods (ie, rTMS and ECT) are reserved for sufferers with therapy resistance, whereas numerous forms of psychotherapy are beneficial for these with MDD.
Whereas value is a crucial think about deciding therapy possibility for sufferers, the RAND/UCLA Appropriateness Technique focuses on the effectiveness of a process and doesn’t take value implication under consideration.60 We additionally acknowledge that the variation of the proposed definition and therapy ideas of PRD in medical follow will probably be influenced by numerous native contexts within the SEA area, together with variations in healthcare system and assets, the provision and accessibility of therapy choices, and monetary constraints and reimbursement system. By and enormous, psychiatry companies can be found in all massive hospitals or medical facilities throughout the SEA area, and thus the implementation of our proposed therapy ideas might be utilized to each inpatient and outpatient settings. These ideas might be carried out in smaller clinics as properly, however this can be restricted by manpower and logistics constraints in monitoring sufferers and sufferers could have to be referred to bigger facilities. In non-public settings, sufferers might be monitored for therapy response extra incessantly, so the therapy timeline might be adjusted to a shorter length. Nonetheless, time and manpower restrictions in public settings could render a shorter follow-up interval troublesome. Skilled medical officers, nurses or junior docs needs to be allowed to hold out therapy monitoring with supervision by the lead psychiatrist to bypass points associated to time and manpower limitations. As such, our proposed ideas and therapy pathway for the administration of MDD and PRD within the SEA area are evidence- and experience-based, and incorporate all accessible remedies, together with newer therapy choices like rTMS and esketamine; these ideas present a practical definition and clear administration steerage for PRD, and might be broadly utilized over the whole SEA area. Within the absence of a regional therapy guideline for PRD that may be employed throughout this broadly heterogenous area, the ideas and pathway we suggest will assist therapy selections for PRD throughout SEA no matter medical settings.
To optimize the administration of sufferers with PRD within the SEA area, now we have developed a consensus on the working definition and therapy ideas of PRD that may be tailored in keeping with numerous native contexts within the SEA international locations. This professional consensus will not be a prescriptive guideline and mustn’t change medical judgement. Particular person circumstances and benefit-risk steadiness needs to be fastidiously thought-about in figuring out essentially the most applicable therapy possibility for sufferers with PRD.
There have been no human topics concerned, and there’s no human materials or identifiable knowledge within the manuscript. As such, institutional overview board or ethics committee approval was not deemed mandatory.
The authors thank Yulyana of In Vivo Communications (Asia) Pte Ltd for the supply of medical writing help within the preparation of this manuscript; funding for this help was offered by Johnson and Johnson Pte Ltd. The authors additionally acknowledge the assist from the Wholesome Pondering Group Asia in performing the literature overview and creating the pre-meeting survey and medical situations for dialogue.
All authors made a big contribution to the work reported, whether or not that’s within the conception, research design, execution, acquisition of information, evaluation and interpretation, or in all these areas; took half in drafting, revising or critically reviewing the article; gave remaining approval of the model to be printed; have agreed on the journal to which the article has been submitted; and conform to be accountable for all features of the work.
All authors acquired honoraria and journey assist from Johnson & Johnson Pte Ltd to attend and take part on the consensus assembly. Pichai Ittasakul has acquired wage assist from Mahidol College, Bangkok, Thailand, lecture honoraria from Janssen, Servier, AstraZeneca, Novartis, Pfizer, Sumitomo Dainippon Pharma. Ahmad Hatim Sulaiman has acquired honoraria as speaker for Johnson & Johnson, participated and acquired grants for medical trial for Johnson & Johnson. Kok Yoon Chee has acquired honoraria as audio system for Johnson & Johnson, Lundbeck, Novartis and Pfizer; participated and acquired investigator charges for medical trial for Johnson & Johnson. Phern Chern Tor, Benita Ponio, Dharmawan Ardi Purnama, Johnson Fam, Elizabeth Rondain, Nurmiati Amir, Roger Ho Chun Man, Wanida Rattanasumawong, Kannokarn Wiroteurairuang and Esketamine is marketed by Janssen, a Johnson & Johnson firm. The authors report no different conflicts of curiosity on this work.
1. GBD 2017 Illness and Damage Incidence and Prevalence Collabolators. International, regional and nationwide incidence, prevalence, and years lived with incapacity for 354 illness and accidents for 195 international locations and territories, 1990–2017: a scientific evaluation for the worldwide burden of illness research 2017. Lancet. 2018;392(10159):1789–1858. doi:10.1016/S0140-6736(18)32279-7
2. Bennabi D, Charpeaud T, Yrondi A, et al. Medical pointers for the administration of treatment-resistant melancholy: french suggestions from specialists, the French Affiliation for organic psychiatry and neuropsychopharmacology and the muse fondaMental. BMC Psychiatry. 2019;19(1):262. doi:10.1186/s12888-019-2237-x
3. Dold M, Kasper S. Proof-based pharmacotherapy of treatment-resistant unipolar melancholy. Int J Psychiatry Clin Pract. 2017;21(1):13–23. doi:10.1080/13651501.2016.1248852
4. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or a number of therapy steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905–1917. doi:10.1176/ajp.2006.163.11.1905
5. Bergfeld IO, Mantione M, Figee M, Schuurman PR, Lok A, Denys D. Remedy-resistant melancholy and suicidality. J Have an effect on Disord. 2018;235:362–367. doi:10.1016/j.jad.2018.04.016
6. Johnston KM, Powell LC, Anderson IM, Szabo S, Cline S. The burden of treatment-resistant melancholy: a scientific overview of the financial and high quality of life literature. J Have an effect on Disord. 2019;242:195–210. doi:10.1016/j.jad.2018.06.045
7. Klug J, Yu F, Chang C, et al. Estimating the financial burden of therapy resistant melancholy in Taiwan utilizing the NHIRD. Worth Well being. 2016;19:A840–1.
8. Souery D, Oswald P, Massat I, et al. Medical elements related to therapy resistance in main depressive dysfunction: outcomes from a European multicenter research. J Clin Psychiatry. 2007;68(7):1062–1070. doi:10.4088/jcp.v68n0713
9. Kubitz N, Vossen C, Papadimitropoulou Okay, Karabis A. The prevalence and illness burden of treatment-resistant melancholy – a scientific overview of the literature. Worth Well being. 2014;17:A455–6.
10. Mahlich J, Tsukazawa S, Wiegand F. Estimating prevalence and healthcare utilization for treatment-resistant melancholy in Japan: a retrospective claims database research. Medication Actual World Outcomes. 2018;5(1):35–43. doi:10.1007/s40801-017-0126-5
11. Fife D, Feng Y, Wang M, et al. Epidemiology of pharmaceutically handled melancholy and therapy resistant melancholy in Taiwan. Psychiatry Res. 2017;252:277–283. doi:10.1016/j.psychres.2017.03.006
12. Ng CH, Kato T, Han C, et al. Definition of treatment-resistant melancholy – Asia Pacific views. J Have an effect on Disord. 2019;245:626–636. doi:10.1016/j.jad.2018.11.038
13. Fife D, Reps J, Cepeda MS, Stang P, Blacketer M, Singh J. Remedy resistant melancholy incidence estimates from research of medical health insurance databases rely strongly on the small print of the working definition. Heliyon. 2018;4(7):e00707. doi:10.1016/j.heliyon.2018.e00707
15. Voineskos D, Daskalakis ZJ, Blumberger DM. Administration of treatment-resistant melancholy: challenges and techniques. Neuropsychiatr Dis Deal with. 2020;16:221–234. doi:10.2147/NDT.S198774
16. Bauer M, Pfennig A, Severus E, Whybrow PC, Angst J, Moller HJ; World Federation of Societies of Organic Psychiatry, Job Drive on Unipolar Depressive Problems. World Federation of Societies of Organic Psychiatry (WFSBP) pointers for organic therapy of unipolar depressive issues, half 1: replace 2013 on the acute and continuation therapy of unipolar depressive issues. World J Biol Psychiatry. 2013;14(5):334–385. doi:10.3109/15622975.2013.804195
17. Kennedy SH, Lam RW, McIntyre RS, et al. Canadian Community for Moon and Nervousness Therapies (CANMAT) 2016 medical pointers for the administration of adults with main depressive dysfunction: part 3. Pharmacological remedies. Can J Psychiatry. 2016;61(9):540–560. doi:10.1177/0706743716659417
18. Malhi GS, Bassett D, Boyce P, et al. Royal Australian and New Zealand Faculty of Psychiatrists medical follow pointers for temper issues. Aust N Z J Psychiatry. 2015;49(12):1087–1206. doi:10.1177/0004867415617657
19. Cleare A, Pariante CM, Younger AH, et al. Proof-based pointers for treating depressive issues with antidepressants: a revision of the 2008 British Affiliation for Psychopharmacology pointers. J Psychopharmacol. 2015;29(5):459–525. doi:10.1177/0269881115581093
23. Chongsuvivatwong V, Phua KH, Yap MT, et al. Well being and health-care methods in Southeast Asia: range and transitions. Lancet. 2011;377(9793):429–437.
24. Nair R, Aggarwal R, Khanna D. Strategies of formal consensus in classification/diagnostic standards and guideline improvement. Semin Arthritis Rheum. 2011;41(2):95–105. doi:10.1016/j.semarthrit.2010.12.001
25. Brown S, Rittenbach Okay, Cheung S, McKean G, MacMaster FP, Clement F. Present and customary definitions of treatment-resistant melancholy: findings from a scientific overview and qualitative interviews. Can J Psychiatry. 2019;64(6):380–387. doi:10.1177/0706743719828965
26. Kraus C, Kadriu B, Lanzenberger R, Zarate CA Jr, Kasper S. Prognosis and improved outcomes in main melancholy: a overview. Transl Psychiatry. 2019;9(1):127. doi:10.1038/s41398-019-0460-3
27. Philip MS, Carpenter LL, Tyrka AR, Worth LH. Pharmacologic approaches to therapy resistant melancholy: a re-examination for the trendy period. Skilled Opin Pharmacother. 2010;11(5):709–722. doi:10.1517/14656561003614781
28. Rush AJ, Trivedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for melancholy. N Engl J Med. 2006;354:1231–1242. doi:10.1056/NEJMoa052963
29. Schosser A, Serretti A, Souery D, et al. European Group for the Research of Resistant Despair (GSRD)–where have we gone thus far: overview of medical and genetic findings. Eur Neuropsychopharmacol. 2012;22:453–468. doi:10.1016/j.euroneuro.2012.02.006
30. Bschor T, Baethge C. No proof for switching the antidepressant: systematic overview and meta-analysis of RCTs of a standard therapeutic technique. Acta Psychiatr Scand. 2010;121:174–179. doi:10.1111/j.1600-0447.2009.01458.x
31. Papakostas GI, Fava M, Thase ME. Remedy of SSRI-resistant melancholy: a meta-analysis evaluating within- versus across-class switches. Biol Psychiatry. 2008;63(7):699–704. doi:10.1016/j.biopsych.2007.08.010
32. Malhi GS, Hitching R, Berk M, Boyce P, Porter R, Fritz Okay. Pharmacological administration of unipolar melancholy. Acta Psychiatr Scand Suppl. 2013;443:6–23. doi:10.1111/acps.12122
33. Tundo A, de Filippis R, Proietti L. Pharmacologic approaches to therapy resistant melancholy: evidences and private expertise. World J Psychiatry. 2015;5(3):330–341. doi:10.5498/wjp.v5.i3.330
35. Somani A, Kar SK. Efficacy of repetitive transcranial magnetic stimulation in treatment-resistant melancholy: the proof to date. Gen Psychiatr. 2019;32(4):e100074. doi:10.1136/gpsych-2019-100074
36. Gaynes BN, Lloyd SW, Lux L, et al. Repetitive transcranial magnetic stimulation for treatment-resistant melancholy: a scientific overview and meta-analysis. J Clin Psychiatry. 2014;75(5):477–89;quiz 489. doi:10.4088/JCP.13r08815
37. Wei Y, Zhu J, Pan S, Su H, Li H, Wang J. Meta-analysis of the efficacy and security of repetitive transcranial magnetic stimulation (rTMS) within the therapy of melancholy. Shanghai Arch Psychiatry. 2017;29(6):328–342. doi:10.11919/j.issn.1002-0829.217106
38. Well being High quality Ontario. Repetitive transcranial magnetic stimulation for treatment-resistant melancholy: a scientific overview and meta-analysis of randomized managed trials. Ont Well being Technol Assess Ser. 2016;16(5):1–66.
39. Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet. 2009;373(9665):746–758.
40. Janicak PG, O’Reardon JP, Sampson SM, et al. Transcranial magnetic stimulation within the therapy of main depressive dysfunction: a complete abstract of security expertise from acute publicity, prolonged publicity and through reintroduction therapy. J Clin Psychiatry. 2008;69(2):222–232. doi:10.1016/S0140-6736(09)60046-5
41. Hansen PE, Ravnkilde B, Videbech P, et al. Low-frequency repetitive transcranial magnetic stimulation inferior to electroconvulsive remedy in treating melancholy. J ECT. 2011;27(1):26–32. doi:10.1097/YCT.0b013e3181d77645
42. Berlim MT, Van den Eynde F, Daskalakis ZJ. Efficacy and acceptability of excessive frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive remedy (ECT) for main melancholy: a scientific overview and meta-analysis of randomized trials. Depress Nervousness. 2013;30(7):614–623. doi:10.1002/da.22060
43. Ren J, Li H, Palaniyappan L, et al. Repetitive transcranial magnetic stimulation versus electroconvulsive remedy for main melancholy: a scientific overview and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2014;51:181–189. doi:10.1016/j.pnpbp.2014.02.004
44. Track GM, Tian X, Shuai T, et al. Remedy of adults with treatment-resistant melancholy: electroconvulsive remedy plus antidepressant or electroconvulsive remedy alone? Proof from an oblique comparability meta-analysis. Drugs. 2015;94(26):e1052. doi:10.1097/MD.0000000000001052
45. Milev RV, Giacobbe P, Kennedy SH, et al. Canadian Community for Temper and Nervousness Therapies (CANMAT) 2016 medical pointers for the administration of adults with main depressive dysfunction: part 4. Neurostimulation remedies. Can J Psychiatry. 2016;61(9):561–575. doi:10.1177/0706743716660033
46. Abdelnaim MA, Langguth B, Deppe M, et al. Anti-suicidal efficacy of repetitive transcranial magnetic stimulation in depressive sufferers: a retrospective evaluation of a giant pattern. Entrance Psychiatry. 2020;10:929. doi:10.3389/fpsyt.2019.00929
47. Desmyter S, Duprat R, Baeken C, Van Autreve S, Audenaert Okay, van Heeringen Okay. Accelerated intermittent theta burst stimulation for suicide danger in therapy-resistant depressed sufferers: a randomized, sham-controlled trials. Entrance Hum Neurosci. 2016;10:480. doi:10.3389/fnhum.2016.00480
48. Weissman MM, Markowitz JC. The way forward for psychotherapies for temper issues. World Psychiatry. 2003;2(1):9–13.
49. Ijaz S, Davies P, Williams CJ, Kessler D, Lewis G, Wiles N. Psychological therapies for treatment-resistant melancholy in adults. Cochrane Database Syst Rev. 2018;5:CD010558. doi:10.1002/14651858.CD010558.pub2
52. Bozymski KM, Crouse EL, Titus-Lay EN, Ott CA, Nofziger JL, Kirkwood CK. Esketamine: a novel possibility for treatment-resistant melancholy. Ann Pharmacother. 2020;54(6):567–576. doi:10.1177/1060028019892644
53. Bahr R, Lopez A, Rey JA. Intranasal Esketamine (SpravatoTM) to be used in treatment-resistant melancholy at the side of an oral antidepressant. Pharm Ther. 2019;44(6):340–375.
54. Kryst J, Kawalec P, Pilc A. Efficacy and security of intranasal esketamine for the therapy of main depressive dysfunction. Skilled Opin Pharmacother. 2020;21(1):9–20. doi:10.1080/14656566.2019.1683161