The perspectives of patients with lithium-induced end-stage renal disease

The perspectives of patients with lithium-induced end-stage renal disease Background: Lithium is the treatment of choice for patients suffering from bipolar disorder (BD) but prolonged use induces renal dysfunction in at least 20% of patient. Intensive monitoring of kidney functioning helps to reveal early decline in renal failure. This study investigates the views and experiences of BD patients who have developed end- stage renal disease and were receiving renal replacement therapy. Results: The patients overall reported not to have been offered alternative treatment options at the start of lithium therapy or when renal functions deteriorated. All indicated to have lacked sound information and dialogue in accord- ance with shared decision making. Kidney monitoring was inadequate in many cases and decision making rushed. Conclusions: Retrospectively, the treatment and monitoring of lithium and the information process were inadequate in many cases. We give suggestions on how to inform patients taking lithium for their BD timely and adequately on the course of renal function loss in the various stages of their treatment. Background improvement or stabilisation of renal function when lith- As it can be very effective in the acute phase and main - ium therapy is discontinued at a renal clearance of 40 ml/ tenance of bipolar disorder (BD), and in the prevention min (Presne et  al. 2003; Lepkifker et  al. 2004). But what of suicide, lithium therapy (LT) is considered the treat- to do when clearance of 40 ml/min or lower or progres- ment of choice for BD (Goodwin et al. 2016; Miura et al. sive loss of 5 ml/min per year indicates LT cessation while 2014; Cipriani et al. 2005). Lithium exposure is associated such an interruption carries a high risk of recurrence of with an increased diagnostic incidence of moderate renal the bipolar disorder. What to recommend patients facing impairment. About 20% of patients on prolonged lith- the dilemma of progression to ESRD and renal replace- ium therapy (LT) develop chronic kidney disease (CKD) ment therapy (RRT) or acute episodes? (Bendz et  al. 2010), Nielsen et  al. recently reviewed the data on development of end-stage renal disease (ESRD) Patient‑centred care and showed they are diverse, from a rate of 5.3/1000 in Clinicians, patients, and others involved in their care and older studies compared to no difference in prevalence in personal life typically base their treatment choices on sci- more recent studies (Nielsen et  al. 2018). The improved entific knowledge, clinical experience, and the patient’s renal outcome in the recent studies might be due to cur- values and preferences (Oxman et  al. 2001). Due to its rently improved renal monitoring and a better focus onset in early adulthood, its episodic course, the patient’s serum lithium levels in patients with renal failure. and family’s accumulating experience with and insight The renal complications warrant monitoring of kid - into individual manifestations and disease course, patient ney functions. International nephrology guidelines rec- involvement tends to be high in BD, with patients exhib- ommend discontinuation of LT in patients with a GFR iting a high sense of responsibility for treatment deci- < 60  ml/min per 1.73  m , with the majority showing sions. Although the patient’s perspective hence deserves a leading role in the treatment of this potentially devas- tating disorder, studies reporting patient experiences *Correspondence: k.grootens@reiniervanarkel.nl with BD and LT are rare (Fisher et al. 2017). Reinier van Arkel, ‘s-Hertogenbosch, The Netherlands Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 2 of 7 LT and ESRD from the patients’ perspective Results Most patients and clinicians are aware of the effec - Patients tiveness of LT on quality of life but also of its longer- Ten patients diagnosed with BP and LT-induced ESRD term risks. A minority of patients will develop CKD receiving RRT were invited by their nephrologists to take and some even ESRD with prolonged use, rendering part in the present study; all ten agreed to participate. The active monitoring for signs of renal involvement indis- participants’ mean age was 71 years (range: 61–88 years) pensable. In this study we focus on the experiences of with nine patients being female. The sample was diverse. patients with LT-induced ESRD receiving RRT. What Eight patients were receiving outpatient haemodialysis, are their views on the consequences of their often one patient was scheduled to start haemodialysis shortly, prolonged LT? Do their reports on treatment choices and one patient was receiving peritoneal dialysis. One of reflect shared decision making? Did they receive sound the patients was shortly to receive a kidney transplant information on the pros and cons of LT to base their while another was scheduled for home haemodialysis. decisions on? Did they know of the risks of CKD, ESRD, Three patients were residents of assisted living facilities. and RRT and what was their attitude towards these Table  1 lists the answers per patient for three decision- potential adverse effects? Were they actively involved making stages: at the start of LT, at the first signs of renal in the choice of treatment strategies? Were they ever insufficiency and when renal failure was diagnosed. The faced with the dilemma of stopping successful LT at the table also shows the patients’ insight into their mental ill- cost of a raised recurrence risk? We are unaware of any ness or psychiatric symptoms and their experiences with study of ESRD patients reporting on these aspects. In renal function monitoring. this study we posed these important questions to ten The patients’ views on LT are distinctly diverse, with such patients. four patients reporting negative experiences voicing a fervent wish to have the drug banned or strongly prefer- Methods ring the agent to no longer be prescribed. Patients “When I started taking lithium, I developed a whole The Dutch register of RRT patients was consulted for BD host of side effects,… but at some point I still agreed to patients with LT-induced ESRD. Ten patients were sub- continue when it proved to do a good job”- patient 2. sequently interviewed of whom informed consent was obtained to audiotape the interviews for later analysis “I developed kidney problems, not by my own doing and to use anonymous quotations. but through the medication for crying out loud, and which I find very hard to deal with”- patient 6 Interviews The first author (AK) gauged the patients’ experi - Those with a more moderate view indicated they ences during a semi-structured interview lasting a thought it was a good drug but that it should not be pre- mean of 51  min. The following topics were addressed: scribed for uninterrupted long-term use or that another (1) information received about the diagnosis and LT, drug should be tested first, with lithium being prescribed (2) information received about adverse effects of LT, only when the former agent proved ineffective. (3) experiences with RRT, and (4) suggestions for BD “Lithium is good, but not for such a long period”- patients facing similar dilemmas. The content of the patient 10. interview was jointly determined by the authors in two consensus meetings. All authors are clinicians with experience with the topic and working in lithium treat- Treatment of bipolar disorder ment units specialised in the care for CKD and ESRD Mean age at BD diagnosis was 40.4  years (range: patients (KG, EH) or delivering RRT (AK). After the 30–62  years). Before they were started on lithium, third interview, we re-evaluated the content, without six patients had been hospitalised. In eight of our ten making any modifications except for change in the order patients a psychiatrist was involved in initiating and of the questions. monitoring LT, while in the other two this was done by their GPs. Average duration of LT was 25  years (range: Quality analysis 6–43 years), during which period four patients had expe- The interview recordings were coded for thematic labels rienced lithium intoxication. Two patients were unable to by AK and subsequently validated by KG and EH. The explain why they had been or were taking lithium. Eight patients were asked to validate their answers to avoid indicated the drug to work well while one patient could misinterpretation. The results are presented in the order not distinguish its effects from those of a previous drug in which the themes were mentioned above. that had also been effective. Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 3 of 7 Table 1 Interview results per patient No patients Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10 Stage 1: start of lithium therapy (LT ) Is patient aware of his/her BD diagnosis? 9/10 Yes Yes Yes Yes Yes Yes Yes No Yes Yes Did psych explain diagnosis? 6/10 No No Yes Yes Yes Yes Yes No Yes No Did psych discuss treatment options? 0/10 No No No No No No No No No No Could patient and/or family indicate own views/standards relevant 1/10 No No No No No Yes No No No No for treatment decision? Who took treatment decision? 10/10 Psych Psych Psych Psych Psych Psych Psych Psych Psych Psych Satisfied with decision-making process? 3/10 No No No No Yes Yes No No Yes No Stage 2: first signs of renal dysfunction/insufficiency Did psych/GP explain clinical problem? 4/6 No n.a. No n.a. Yes n.a. Yes Yes Yes n.a. Was neph involved at this stage? 4/6 Yes No ? No Yes No Yes No Yes No Did psych/GP discuss alternatives to LT? 0/6 No n.a. No n.a. No n.a. No No No n.a. Could own views/standards be given for consideration in treat- 1/6 No n.a. No n.a. No n.a. No No Yes n.a. ment decision? Who took treatment decision? neph n.a. Psych n.a. Psych n.a. Shared Psych Shared n.a. Psych/neph/patient/shared decision Satisfied with decision-making process? 4/6 Yes n.a. ? n.a. No n.a. Yes No Yes n.a. Stage 3: renal failure Did psych/GP/neph explain situation? 8/10 Yes Yes Yes Yes Yes No Yes Yes Yes No Did psych/GP discuss alternatives to LT/? 2/10 No Yes No No Yes No No No No No Could own views/standards be given for consideration in treat- 4/10 No No Yes No Yes No Yes No Yes No ment decision? Who took treatment decision? Psych Psych Shared Psych Shared Psych Shared Psych Shared neph Psych/neph/patient/shared decision Satisfied with decision-making process? 5/10 Yes No Yes No Yes No Yes No Yes No Psychiatric items Is patient able to explain severity of BD symptoms? 9/10 Yes Yes Yes Yes Yes Yes Yes No Yes Yes Was indication for LT according to clinical guidelines? 8/10 No Yes Yes Yes Yes Yes ? Yes Yes Yes Is patient able to explain why s(he) is/was taking lithium? 8/10 No Yes Yes Yes Yes Yes Yes No Yes Yes Were side effects of lithium explained? 1/10 No Yes No No No No No No No No Nephrological follow-up lithium Was kidney function checked at least 2x/year? 8/10 Yes No Yes Yes Yes Yes Yes Yes No Yes Were lithium levels checked every 6 months? 9/10 Yes Yes Yes Yes Yes Yes Yes Yes No Yes Psych psychiatrist, GP general practitioner, neph nephrologist, n.a. not applicable (e.g. because this stage//symptoms went undetected), ? unknown to patient, LT lithium therapy Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 4 of 7 “If I don’t take lithium I get anxious that I’ll get treatment options being discussed. When ESRD was manic or depressed and I don’t want that”- patient 9 diagnosed, however, patients and family members were more actively involved in treatment decisions. Three patients were still taking lithium at the time of the interview or had restarted LT, one of whom had not “I asked if I could start taking lithium again, and the been offered an alternative after LT discontinuation, kidney specialist and psychiatrist jointly decided I while in one the new agent was less effective and LT was could”- patient 3 restarted. The third patient had stayed on lithium for fear of a manic relapse. “My psychiatrist got in touch with the nephrologist and, with our kids there, we all got to thinking that “They decided to stop prescribing lithium when they restarting lithium would be a good thing to do”- found out that my kidneys were acting up. But I got patient 5 terribly depressed.. got into a deep depression, which is why we jointly decided that I should start taking it “If I would start feeling anxious again, I know I can again”- patient 3 ask to have me restarted on lithium”- patient 7 The remaining seven patients no longer took lithium. One patient experienced a manic episode after LT cessa- Patient recommendations for clinicians and fellow tion without receiving replacement therapy. After start- or future patients ing a new regimen, the patient’s mental state stabilised. Asked what could be done to improve patient education Five patients were clear in indicating that after LT discon- and information, most of the interviewees (6/10) rec- tinuation they had experienced no relapses while being ommended to provide more information about lithium on an alternative agent. Two no longer took any psycho- including its adverse effects. It was further recommended tropic medication and had remained symptom-free. (2/10) to take someone with you to such appointments and that during the consultation the patient should be Experiences with kidney failure and RRT offered a choice of treatments (2/10). It was additionally Nine of the interviewees were receiving RRT, with a mean suggested that a hand-out might be useful, to allow some of 2.6 years (range: 1 month to 10 years). None had experi- time between the visit and the decision, and to possibly enced an increase in bipolar symptoms when first starting follow-up on the discussion every one or 2 years. haemodialysis. One patient was admitted after 6  months of dialysis on account of a psychotic depression. Despite “I didn’t get no information or anything, I wish they’d reporting various RRT-related problems, such as shunt explained things to me” - patient 1 problems and time burden, the majority (7/9) indicated having grown used to RRT and feeling well. “I want to hear what medicine he’s going to give me. And that he says: you have this medicine, and this “I have such a huge fear of blood… and I needed to and another. And this one works like this and the press the shunt for such a long time! 45  min or even other one like so. And that you can choose”- patient 6 longer”- patient 3 Four patients furthermore hoped that patients first “I could not sit… the pain when they put the needle being prescribed lithium will be monitored better. Two in - leaning back makes you feel really sick”- patient 8 patients expressed a wish for more visits and dialogue rather than pills, while new patients are advised to be well aware of the consequences of LT. Finally, the advice Information on lithium and kidney‑function to first try another drug treatment was offered frequently. monitoring None of the interviewees remembered having been “Talk to patients more, don’t just give them a pill offered a choice in treatments when starting lithium right away”- patient 1 (Table  1). Accordingly, all viewed the decision to start LT as paternalistic, with a sense of discontent being most “You can’t go and drug patients up just like that… pronounced. Only one patient reported having been you need to communicate”- patient 8 informed about the side effects of lithium (Table 1). Kidney function and lithium levels were monitored reg- Discussion ularly in seven patients. At the time when serious dete- To our knowledge, ours is the first survey to report on the rioration of renal functions was established (which stage experiences of ten patients with bipolar disorder and lith- was identified in six of the ten patients by the attend - ium-induced end-stage renal failure. Since the literature ing clinician), again, none of the patients remembered Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 5 of 7 on the specific wishes of patients with regard to BD treat - the current descriptions of their medical history and the ments is limited (Fisher et  al. 2017), we purposely con- roles of themselves and their doctor. tacted patients who were likely to be dissatisfied with the Unfortunately, these confounders also prevent us from results of their treatment to learn from their experiences. asking the attending clinicians to consider their treat- ment decisions in retrospect. Patients want to be given options Although small-scale and explorative, our study did Recommendations yield clear patient preferences regarding the decision- Kidney dysfunction is not always preventable and some- making process. The majority of the patients we inter - times renal replacement therapy is accepted as part of the viewed labelled the information they had received about deal because lithium is indispensable for the patient con- the treatment of their BD and the treatment decision as cerned. The ultimate decision should always be tailored paternalistic. Even though at the time they had given their to the individual. In today’s clinical practice the final informed consent, they all indicated they would have pre- decision lies with the patient and not with the clinician. ferred to have been more involved in the decision to start It is then crucial that each patient is well informed about LT. In addition to more information on lithium, more ‘lithium and the kidney’ to enable them to make sound options should have been discussed in terms of the bene- decisions as to their treatment. Patients with complex fits and disadvantages of different medications, refraining mood disorders often have symptom-free intervals dur- from medication, psychotherapy, or lower doses. ing which they are receptive for detailed, targeted infor- It is plausible to assume that when our patients were mation and instructions while those closely involved in first started on LT, open discussions about treatment the patient’s life may be invited to also attend such visits. options was not the commonplace practice it is today. Since the course of renal function loss tends to be insidi- Still, whether in today’s consulting rooms shared decision ous, there is no urgent need to acutely cease LT or switch making is truly shared and on an equal par still is a ques- to another agent, allowing all parties sufficient time to tion of debate (Verwijmeren and Grootens, under review; make informed decisions and try out different regimens. Alguera-Lara et al. 2017). Patients not always make well- In Table 2 we offer recommendations on LT and poten - balanced rational decisions; they also base their decisions tial renal effects. We have adopted a nuanced approach on the views of their doctors in whom they have put their in which we have incorporated the patient’s perspective, trust (Fraenkel and McGraw 2007). Another recent BD which is in contrast to the current nephrological guide- study found that it primarily are clinician-related factors lines that stipulate to discontinue lithium ‘top down’ that determine treatment modalities, whereby patient with a GFR < 60 in the presence of an intercurrent illness preferences play a lesser role (Fisher et  al. 2017). This that increases the risk of acute renal failure. We distin- practice thus contradicts the wish for shared decision guish three stages during LT, with stage 1 comprising the making patients express (Fisher et al. 2017; Alguera-Lara start of the treatment, stage 2 the first signs of mild to et al. 2017). moderate reduction in renal functions (GFR 45–59  ml/ min/1.73m ), and stage 3 the moment severe renal insuf- Limitations ficiency or failure is diagnosed. In our recommendations Our study has several limitations. It firstly suffers from a we merely provide cues for what needs to be done and, as selection bias in that for the vast majority of people liv- yet, not how to do so or which alternatives can or should ing with BD lithium is effective and has no nephrogenic be considered. We invite all parties to participate in ini- effects. Moreover, patient preferences may change in the tiatives that will help us enhance the knowledge and deci- course of the illness (Hajda et  al. 2016). We interviewed sion-making skills regarding lithium for both patients patients who had undergone all treatment phases and and clinicians. were asked to retrospectively contemplate what would have been the optimal process, which ideas may have dif- Quality of treatment fered from those at the time they first started LT, while It needs to be noted that we conducted our survey in recall bias could have affected outcome determination. the Netherlands, a densely populated and wealthy coun- Some of the events were a long time ago, and it is a well- try sporting numerous lithium outpatient clinics and a known fact that patients cannot remember all what is national network of knowledge centres in which patients explained and told in the consulting room. Though, in and patient associations actively participate. With two cases, the spouse participated in the interview and our study we have no intention of praising or criticis- confirmed the answers given by the patient. Further - ing our national healthcare policies. Our only aim is to more, high emotional levels and psychodynamic defence give a small group of patients a voice and to learn from mechanisms (such as denial) may have contributed to them. Nonetheless, in retrospect, treatment decisions Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 6 of 7 Table 2 Recommendations for health professionals regarding lithium therapy and potential renal complications Stage 1: Start lithium therapy Discuss symptoms/course of mental disorder and provide information on lithium and treatment (GFR > 60 ml/min/1.73 m ) options on a regular basis Relevant for all patients on lithium Discuss lithium-related complications such as nephrogenic diabetes insipidus and renal failure (esp. in euthymic phase) Discuss lifestyle factors (smoking, body weight) Provide information about lithium use (dose/duration), prevention of intoxication, and how to act in case of dehydration Initiate lithium and kidney monitoring in accordance with (inter)national guidelines Attending health professional(s) should recognise and act on first signs of declining renal function at an early stage (i.e. increasing creatinine levels but also decreasing GFR) Stage 2: First signs of renal dysfunction Attending health professional(s) should recognise and act on first signs of declining renal function (GFR 40-60 ml/min/1.73 m ) at an early stage (i.e. increasing creatinine levels but also decreasing GFR) Relevant for 12% of patients taking lithium Intensify monitoring Obtain advice from or refer for treatment to experts in the field of lithium-induced nephropathy (preferably a nephrologist and psychiatrist) Explain end-stage renal disorder, prognosis, and implications of haemodialysis Discuss all pros and cons of all relevant treatment options with patient and family (e.g. continuing lithium therapy, tapering lithium, switching to another drug) Take into consideration that renal dysfunction will progress at GFR < 40 (‘point of no return’).(5) Stage 3: Severe renal insufficiency and renal failure Treatment by psychiatrist and nephrologist (GFR < 25 ml/min/1.73 m ) If lithium is discontinued: review regularly whether lithium should be restarted. Relevant for 12‰ to approx. 1% of lithium users Abbreviations and delivery might have been different. Two of the ten BD: bipolar disorder; CKD: chronic kidney disease; ESRD: end stage renal LTs were not monitored by a psychiatrist and it was still disease; GFR: glomura; LT: lithium therapy. decided to taper lithium or to switch to another mood Authors’ contributions stabiliser. All authors contributed to the study design, data interpretation and the It is of the utmost importance that LT is delivered and writing of the manuscript. Author AK localised the patients and visited the monitored by psychiatrists who, in addition to symp- patients for the interviews, and wrote the first draft of the manuscript. All authors read and approved the final manuscript. tom-contingent cues, can also identify and discuss time- contingent complaints with their patient and can keep Authors’ information in close contact with the attending nephrologist. It is in The authors are a nephrologist and two psychiatrists (two of them are also registered as clinical pharmacologist) with clinical experience in treating the patients’ best interest that they are seen at a lithium bipolar patients with lithium induced renal side effects. They take part in a clinic that is equipped to identify the absence of (regular) Dutch research consortium of scientists working on the renal side effect of renal monitoring and detect insidious renal dysfunction lithium treatment. in a timely manner, and where staff has expert knowledge Author details about lithium-induced renal damage so that they can be 1 2 Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands. CWZ Hospital, optimally informed about the options available to them. Nijmegen, The Netherlands. Reinier van Arkel, ‘s-Hertogenbosch, The Nether- lands. Radboudumc, Nijmegen, The Netherlands. Our survey demonstrates that this is exactly what the patients who have to cope with a serious mood disorder Acknowledgements on a daily basis want and expect. No acknowledgment. Competing interests Conclusions No competing interest. • This is the first paper that focuses on the opinions of Availability of data and materials lithium patients who developed end stage renal dis- Data can be shared, please contact the corresponding author. ease. • Retrospectively, the treatment and monitoring of Consent for publication Patients gave consent for publication. lithium and the information process were inadequate in many cases. Ethics approval and consent to participate • We give suggestions on how to inform patients tak- The study was approved by the Reinier van Arkel ethical committee. ing lithium for their BD timely and adequately on the Funding course of renal function loss in the various stages of No funding. their treatment. Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 7 of 7 Fraenkel L, McGraw S. Participation in medical decision making: the patients’ Publisher’s Note perspective. Med Decis Making. 2007;27(5):533–8. Springer Nature remains neutral with regard to jurisdictional claims in pub- Goodwin GM, Haddad PM, Ferrier IH, et al. Evidence-based guidelines for lished maps and institutional affiliations. treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. Received: 6 February 2018 Accepted: 21 March 2018 2016;30(6):495–553. Hajda M, Prasko J, Latalova K, et al. Unmet needs of bipolar disorder patients. Neuropsychiatr Dis Treat. 2016;12:1561–70. Lepkifker E, Sverdlik A, Iancu I, et al. Renal insufficiency in long-term lithium treatment. J Clin Psychiatry. 2004;65:850–6. References Miura T, Noma H, Furukawa TA, et al. Comparative efficacy and tolerability of Alguera-Lara V, Dowsey MM, Ride J, Kinder S, Castle D. Shared decision making pharmocological treatments in the maintenance treatment of bipolar in mental health: the importance for current clinical practice. Australas disorder: a systematic review and network meta-analysis. Lancet Psychia- Psychiatry. 2017;25(6):578–82. try. 2014;1(5):351–9. Bendz H, Schon S, Attman PO, et al. Renal failure occurs in chronic lithium Nielsen RE, Kessing LV, Nolen WA, Licht RW. Lithium and renal impairment: a treatment but is uncommon. Kidney Int. 2010;77:219–24. review on a still hot topic. Pharmacopsychiatry. 2018. https://doi.org/10.1 Cipriani A, Pretty H, Hawton K, Geddes JR. Lithium in the prevention of suicidal 055/s-0043-125393. behavior and all-cause mortality in patients with mood disorders: a sys- Oxman AD, Chalmers I, Sackett DL. A practical guide to informed consent to tematic review of randomized trials. Am J Psychiatry. 2005;162:1805–19. treatment. BMJ. 2001;323(7327):1464–6. Fisher A, et al. A qualitative exploration of clinician views and experiences Presne C, Fakhouri F, Noel LH, et al. Lithium-induced nephropathy: rate of of treatment decision-making in bipolar II disorder. Community Ment progression and prognostic factors. Kidney Int. 2003;64:585–92. Health J. 2017b;53(8):958–71. Verwijmeren D, Grootens KP. Shared decision making in pharmacotherapy Fisher A, Manicavasagar V, Sharpe L, et al. Qualitative exploration of patient decisions, perceived by patients with bipolar disorder. (under review). and family views and experiences of treatment decision-making in bipo- lar II disorder. J Mental Health. 2017a;27(1):66–79. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Bipolar Disorders Springer Journals

The perspectives of patients with lithium-induced end-stage renal disease

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Abstract

Background: Lithium is the treatment of choice for patients suffering from bipolar disorder (BD) but prolonged use induces renal dysfunction in at least 20% of patient. Intensive monitoring of kidney functioning helps to reveal early decline in renal failure. This study investigates the views and experiences of BD patients who have developed end- stage renal disease and were receiving renal replacement therapy. Results: The patients overall reported not to have been offered alternative treatment options at the start of lithium therapy or when renal functions deteriorated. All indicated to have lacked sound information and dialogue in accord- ance with shared decision making. Kidney monitoring was inadequate in many cases and decision making rushed. Conclusions: Retrospectively, the treatment and monitoring of lithium and the information process were inadequate in many cases. We give suggestions on how to inform patients taking lithium for their BD timely and adequately on the course of renal function loss in the various stages of their treatment. Background improvement or stabilisation of renal function when lith- As it can be very effective in the acute phase and main - ium therapy is discontinued at a renal clearance of 40 ml/ tenance of bipolar disorder (BD), and in the prevention min (Presne et  al. 2003; Lepkifker et  al. 2004). But what of suicide, lithium therapy (LT) is considered the treat- to do when clearance of 40 ml/min or lower or progres- ment of choice for BD (Goodwin et al. 2016; Miura et al. sive loss of 5 ml/min per year indicates LT cessation while 2014; Cipriani et al. 2005). Lithium exposure is associated such an interruption carries a high risk of recurrence of with an increased diagnostic incidence of moderate renal the bipolar disorder. What to recommend patients facing impairment. About 20% of patients on prolonged lith- the dilemma of progression to ESRD and renal replace- ium therapy (LT) develop chronic kidney disease (CKD) ment therapy (RRT) or acute episodes? (Bendz et  al. 2010), Nielsen et  al. recently reviewed the data on development of end-stage renal disease (ESRD) Patient‑centred care and showed they are diverse, from a rate of 5.3/1000 in Clinicians, patients, and others involved in their care and older studies compared to no difference in prevalence in personal life typically base their treatment choices on sci- more recent studies (Nielsen et  al. 2018). The improved entific knowledge, clinical experience, and the patient’s renal outcome in the recent studies might be due to cur- values and preferences (Oxman et  al. 2001). Due to its rently improved renal monitoring and a better focus onset in early adulthood, its episodic course, the patient’s serum lithium levels in patients with renal failure. and family’s accumulating experience with and insight The renal complications warrant monitoring of kid - into individual manifestations and disease course, patient ney functions. International nephrology guidelines rec- involvement tends to be high in BD, with patients exhib- ommend discontinuation of LT in patients with a GFR iting a high sense of responsibility for treatment deci- < 60  ml/min per 1.73  m , with the majority showing sions. Although the patient’s perspective hence deserves a leading role in the treatment of this potentially devas- tating disorder, studies reporting patient experiences *Correspondence: k.grootens@reiniervanarkel.nl with BD and LT are rare (Fisher et al. 2017). Reinier van Arkel, ‘s-Hertogenbosch, The Netherlands Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 2 of 7 LT and ESRD from the patients’ perspective Results Most patients and clinicians are aware of the effec - Patients tiveness of LT on quality of life but also of its longer- Ten patients diagnosed with BP and LT-induced ESRD term risks. A minority of patients will develop CKD receiving RRT were invited by their nephrologists to take and some even ESRD with prolonged use, rendering part in the present study; all ten agreed to participate. The active monitoring for signs of renal involvement indis- participants’ mean age was 71 years (range: 61–88 years) pensable. In this study we focus on the experiences of with nine patients being female. The sample was diverse. patients with LT-induced ESRD receiving RRT. What Eight patients were receiving outpatient haemodialysis, are their views on the consequences of their often one patient was scheduled to start haemodialysis shortly, prolonged LT? Do their reports on treatment choices and one patient was receiving peritoneal dialysis. One of reflect shared decision making? Did they receive sound the patients was shortly to receive a kidney transplant information on the pros and cons of LT to base their while another was scheduled for home haemodialysis. decisions on? Did they know of the risks of CKD, ESRD, Three patients were residents of assisted living facilities. and RRT and what was their attitude towards these Table  1 lists the answers per patient for three decision- potential adverse effects? Were they actively involved making stages: at the start of LT, at the first signs of renal in the choice of treatment strategies? Were they ever insufficiency and when renal failure was diagnosed. The faced with the dilemma of stopping successful LT at the table also shows the patients’ insight into their mental ill- cost of a raised recurrence risk? We are unaware of any ness or psychiatric symptoms and their experiences with study of ESRD patients reporting on these aspects. In renal function monitoring. this study we posed these important questions to ten The patients’ views on LT are distinctly diverse, with such patients. four patients reporting negative experiences voicing a fervent wish to have the drug banned or strongly prefer- Methods ring the agent to no longer be prescribed. Patients “When I started taking lithium, I developed a whole The Dutch register of RRT patients was consulted for BD host of side effects,… but at some point I still agreed to patients with LT-induced ESRD. Ten patients were sub- continue when it proved to do a good job”- patient 2. sequently interviewed of whom informed consent was obtained to audiotape the interviews for later analysis “I developed kidney problems, not by my own doing and to use anonymous quotations. but through the medication for crying out loud, and which I find very hard to deal with”- patient 6 Interviews The first author (AK) gauged the patients’ experi - Those with a more moderate view indicated they ences during a semi-structured interview lasting a thought it was a good drug but that it should not be pre- mean of 51  min. The following topics were addressed: scribed for uninterrupted long-term use or that another (1) information received about the diagnosis and LT, drug should be tested first, with lithium being prescribed (2) information received about adverse effects of LT, only when the former agent proved ineffective. (3) experiences with RRT, and (4) suggestions for BD “Lithium is good, but not for such a long period”- patients facing similar dilemmas. The content of the patient 10. interview was jointly determined by the authors in two consensus meetings. All authors are clinicians with experience with the topic and working in lithium treat- Treatment of bipolar disorder ment units specialised in the care for CKD and ESRD Mean age at BD diagnosis was 40.4  years (range: patients (KG, EH) or delivering RRT (AK). After the 30–62  years). Before they were started on lithium, third interview, we re-evaluated the content, without six patients had been hospitalised. In eight of our ten making any modifications except for change in the order patients a psychiatrist was involved in initiating and of the questions. monitoring LT, while in the other two this was done by their GPs. Average duration of LT was 25  years (range: Quality analysis 6–43 years), during which period four patients had expe- The interview recordings were coded for thematic labels rienced lithium intoxication. Two patients were unable to by AK and subsequently validated by KG and EH. The explain why they had been or were taking lithium. Eight patients were asked to validate their answers to avoid indicated the drug to work well while one patient could misinterpretation. The results are presented in the order not distinguish its effects from those of a previous drug in which the themes were mentioned above. that had also been effective. Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 3 of 7 Table 1 Interview results per patient No patients Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10 Stage 1: start of lithium therapy (LT ) Is patient aware of his/her BD diagnosis? 9/10 Yes Yes Yes Yes Yes Yes Yes No Yes Yes Did psych explain diagnosis? 6/10 No No Yes Yes Yes Yes Yes No Yes No Did psych discuss treatment options? 0/10 No No No No No No No No No No Could patient and/or family indicate own views/standards relevant 1/10 No No No No No Yes No No No No for treatment decision? Who took treatment decision? 10/10 Psych Psych Psych Psych Psych Psych Psych Psych Psych Psych Satisfied with decision-making process? 3/10 No No No No Yes Yes No No Yes No Stage 2: first signs of renal dysfunction/insufficiency Did psych/GP explain clinical problem? 4/6 No n.a. No n.a. Yes n.a. Yes Yes Yes n.a. Was neph involved at this stage? 4/6 Yes No ? No Yes No Yes No Yes No Did psych/GP discuss alternatives to LT? 0/6 No n.a. No n.a. No n.a. No No No n.a. Could own views/standards be given for consideration in treat- 1/6 No n.a. No n.a. No n.a. No No Yes n.a. ment decision? Who took treatment decision? neph n.a. Psych n.a. Psych n.a. Shared Psych Shared n.a. Psych/neph/patient/shared decision Satisfied with decision-making process? 4/6 Yes n.a. ? n.a. No n.a. Yes No Yes n.a. Stage 3: renal failure Did psych/GP/neph explain situation? 8/10 Yes Yes Yes Yes Yes No Yes Yes Yes No Did psych/GP discuss alternatives to LT/? 2/10 No Yes No No Yes No No No No No Could own views/standards be given for consideration in treat- 4/10 No No Yes No Yes No Yes No Yes No ment decision? Who took treatment decision? Psych Psych Shared Psych Shared Psych Shared Psych Shared neph Psych/neph/patient/shared decision Satisfied with decision-making process? 5/10 Yes No Yes No Yes No Yes No Yes No Psychiatric items Is patient able to explain severity of BD symptoms? 9/10 Yes Yes Yes Yes Yes Yes Yes No Yes Yes Was indication for LT according to clinical guidelines? 8/10 No Yes Yes Yes Yes Yes ? Yes Yes Yes Is patient able to explain why s(he) is/was taking lithium? 8/10 No Yes Yes Yes Yes Yes Yes No Yes Yes Were side effects of lithium explained? 1/10 No Yes No No No No No No No No Nephrological follow-up lithium Was kidney function checked at least 2x/year? 8/10 Yes No Yes Yes Yes Yes Yes Yes No Yes Were lithium levels checked every 6 months? 9/10 Yes Yes Yes Yes Yes Yes Yes Yes No Yes Psych psychiatrist, GP general practitioner, neph nephrologist, n.a. not applicable (e.g. because this stage//symptoms went undetected), ? unknown to patient, LT lithium therapy Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 4 of 7 “If I don’t take lithium I get anxious that I’ll get treatment options being discussed. When ESRD was manic or depressed and I don’t want that”- patient 9 diagnosed, however, patients and family members were more actively involved in treatment decisions. Three patients were still taking lithium at the time of the interview or had restarted LT, one of whom had not “I asked if I could start taking lithium again, and the been offered an alternative after LT discontinuation, kidney specialist and psychiatrist jointly decided I while in one the new agent was less effective and LT was could”- patient 3 restarted. The third patient had stayed on lithium for fear of a manic relapse. “My psychiatrist got in touch with the nephrologist and, with our kids there, we all got to thinking that “They decided to stop prescribing lithium when they restarting lithium would be a good thing to do”- found out that my kidneys were acting up. But I got patient 5 terribly depressed.. got into a deep depression, which is why we jointly decided that I should start taking it “If I would start feeling anxious again, I know I can again”- patient 3 ask to have me restarted on lithium”- patient 7 The remaining seven patients no longer took lithium. One patient experienced a manic episode after LT cessa- Patient recommendations for clinicians and fellow tion without receiving replacement therapy. After start- or future patients ing a new regimen, the patient’s mental state stabilised. Asked what could be done to improve patient education Five patients were clear in indicating that after LT discon- and information, most of the interviewees (6/10) rec- tinuation they had experienced no relapses while being ommended to provide more information about lithium on an alternative agent. Two no longer took any psycho- including its adverse effects. It was further recommended tropic medication and had remained symptom-free. (2/10) to take someone with you to such appointments and that during the consultation the patient should be Experiences with kidney failure and RRT offered a choice of treatments (2/10). It was additionally Nine of the interviewees were receiving RRT, with a mean suggested that a hand-out might be useful, to allow some of 2.6 years (range: 1 month to 10 years). None had experi- time between the visit and the decision, and to possibly enced an increase in bipolar symptoms when first starting follow-up on the discussion every one or 2 years. haemodialysis. One patient was admitted after 6  months of dialysis on account of a psychotic depression. Despite “I didn’t get no information or anything, I wish they’d reporting various RRT-related problems, such as shunt explained things to me” - patient 1 problems and time burden, the majority (7/9) indicated having grown used to RRT and feeling well. “I want to hear what medicine he’s going to give me. And that he says: you have this medicine, and this “I have such a huge fear of blood… and I needed to and another. And this one works like this and the press the shunt for such a long time! 45  min or even other one like so. And that you can choose”- patient 6 longer”- patient 3 Four patients furthermore hoped that patients first “I could not sit… the pain when they put the needle being prescribed lithium will be monitored better. Two in - leaning back makes you feel really sick”- patient 8 patients expressed a wish for more visits and dialogue rather than pills, while new patients are advised to be well aware of the consequences of LT. Finally, the advice Information on lithium and kidney‑function to first try another drug treatment was offered frequently. monitoring None of the interviewees remembered having been “Talk to patients more, don’t just give them a pill offered a choice in treatments when starting lithium right away”- patient 1 (Table  1). Accordingly, all viewed the decision to start LT as paternalistic, with a sense of discontent being most “You can’t go and drug patients up just like that… pronounced. Only one patient reported having been you need to communicate”- patient 8 informed about the side effects of lithium (Table 1). Kidney function and lithium levels were monitored reg- Discussion ularly in seven patients. At the time when serious dete- To our knowledge, ours is the first survey to report on the rioration of renal functions was established (which stage experiences of ten patients with bipolar disorder and lith- was identified in six of the ten patients by the attend - ium-induced end-stage renal failure. Since the literature ing clinician), again, none of the patients remembered Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 5 of 7 on the specific wishes of patients with regard to BD treat - the current descriptions of their medical history and the ments is limited (Fisher et  al. 2017), we purposely con- roles of themselves and their doctor. tacted patients who were likely to be dissatisfied with the Unfortunately, these confounders also prevent us from results of their treatment to learn from their experiences. asking the attending clinicians to consider their treat- ment decisions in retrospect. Patients want to be given options Although small-scale and explorative, our study did Recommendations yield clear patient preferences regarding the decision- Kidney dysfunction is not always preventable and some- making process. The majority of the patients we inter - times renal replacement therapy is accepted as part of the viewed labelled the information they had received about deal because lithium is indispensable for the patient con- the treatment of their BD and the treatment decision as cerned. The ultimate decision should always be tailored paternalistic. Even though at the time they had given their to the individual. In today’s clinical practice the final informed consent, they all indicated they would have pre- decision lies with the patient and not with the clinician. ferred to have been more involved in the decision to start It is then crucial that each patient is well informed about LT. In addition to more information on lithium, more ‘lithium and the kidney’ to enable them to make sound options should have been discussed in terms of the bene- decisions as to their treatment. Patients with complex fits and disadvantages of different medications, refraining mood disorders often have symptom-free intervals dur- from medication, psychotherapy, or lower doses. ing which they are receptive for detailed, targeted infor- It is plausible to assume that when our patients were mation and instructions while those closely involved in first started on LT, open discussions about treatment the patient’s life may be invited to also attend such visits. options was not the commonplace practice it is today. Since the course of renal function loss tends to be insidi- Still, whether in today’s consulting rooms shared decision ous, there is no urgent need to acutely cease LT or switch making is truly shared and on an equal par still is a ques- to another agent, allowing all parties sufficient time to tion of debate (Verwijmeren and Grootens, under review; make informed decisions and try out different regimens. Alguera-Lara et al. 2017). Patients not always make well- In Table 2 we offer recommendations on LT and poten - balanced rational decisions; they also base their decisions tial renal effects. We have adopted a nuanced approach on the views of their doctors in whom they have put their in which we have incorporated the patient’s perspective, trust (Fraenkel and McGraw 2007). Another recent BD which is in contrast to the current nephrological guide- study found that it primarily are clinician-related factors lines that stipulate to discontinue lithium ‘top down’ that determine treatment modalities, whereby patient with a GFR < 60 in the presence of an intercurrent illness preferences play a lesser role (Fisher et  al. 2017). This that increases the risk of acute renal failure. We distin- practice thus contradicts the wish for shared decision guish three stages during LT, with stage 1 comprising the making patients express (Fisher et al. 2017; Alguera-Lara start of the treatment, stage 2 the first signs of mild to et al. 2017). moderate reduction in renal functions (GFR 45–59  ml/ min/1.73m ), and stage 3 the moment severe renal insuf- Limitations ficiency or failure is diagnosed. In our recommendations Our study has several limitations. It firstly suffers from a we merely provide cues for what needs to be done and, as selection bias in that for the vast majority of people liv- yet, not how to do so or which alternatives can or should ing with BD lithium is effective and has no nephrogenic be considered. We invite all parties to participate in ini- effects. Moreover, patient preferences may change in the tiatives that will help us enhance the knowledge and deci- course of the illness (Hajda et  al. 2016). We interviewed sion-making skills regarding lithium for both patients patients who had undergone all treatment phases and and clinicians. were asked to retrospectively contemplate what would have been the optimal process, which ideas may have dif- Quality of treatment fered from those at the time they first started LT, while It needs to be noted that we conducted our survey in recall bias could have affected outcome determination. the Netherlands, a densely populated and wealthy coun- Some of the events were a long time ago, and it is a well- try sporting numerous lithium outpatient clinics and a known fact that patients cannot remember all what is national network of knowledge centres in which patients explained and told in the consulting room. Though, in and patient associations actively participate. With two cases, the spouse participated in the interview and our study we have no intention of praising or criticis- confirmed the answers given by the patient. Further - ing our national healthcare policies. Our only aim is to more, high emotional levels and psychodynamic defence give a small group of patients a voice and to learn from mechanisms (such as denial) may have contributed to them. Nonetheless, in retrospect, treatment decisions Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 6 of 7 Table 2 Recommendations for health professionals regarding lithium therapy and potential renal complications Stage 1: Start lithium therapy Discuss symptoms/course of mental disorder and provide information on lithium and treatment (GFR > 60 ml/min/1.73 m ) options on a regular basis Relevant for all patients on lithium Discuss lithium-related complications such as nephrogenic diabetes insipidus and renal failure (esp. in euthymic phase) Discuss lifestyle factors (smoking, body weight) Provide information about lithium use (dose/duration), prevention of intoxication, and how to act in case of dehydration Initiate lithium and kidney monitoring in accordance with (inter)national guidelines Attending health professional(s) should recognise and act on first signs of declining renal function at an early stage (i.e. increasing creatinine levels but also decreasing GFR) Stage 2: First signs of renal dysfunction Attending health professional(s) should recognise and act on first signs of declining renal function (GFR 40-60 ml/min/1.73 m ) at an early stage (i.e. increasing creatinine levels but also decreasing GFR) Relevant for 12% of patients taking lithium Intensify monitoring Obtain advice from or refer for treatment to experts in the field of lithium-induced nephropathy (preferably a nephrologist and psychiatrist) Explain end-stage renal disorder, prognosis, and implications of haemodialysis Discuss all pros and cons of all relevant treatment options with patient and family (e.g. continuing lithium therapy, tapering lithium, switching to another drug) Take into consideration that renal dysfunction will progress at GFR < 40 (‘point of no return’).(5) Stage 3: Severe renal insufficiency and renal failure Treatment by psychiatrist and nephrologist (GFR < 25 ml/min/1.73 m ) If lithium is discontinued: review regularly whether lithium should be restarted. Relevant for 12‰ to approx. 1% of lithium users Abbreviations and delivery might have been different. Two of the ten BD: bipolar disorder; CKD: chronic kidney disease; ESRD: end stage renal LTs were not monitored by a psychiatrist and it was still disease; GFR: glomura; LT: lithium therapy. decided to taper lithium or to switch to another mood Authors’ contributions stabiliser. All authors contributed to the study design, data interpretation and the It is of the utmost importance that LT is delivered and writing of the manuscript. Author AK localised the patients and visited the monitored by psychiatrists who, in addition to symp- patients for the interviews, and wrote the first draft of the manuscript. All authors read and approved the final manuscript. tom-contingent cues, can also identify and discuss time- contingent complaints with their patient and can keep Authors’ information in close contact with the attending nephrologist. It is in The authors are a nephrologist and two psychiatrists (two of them are also registered as clinical pharmacologist) with clinical experience in treating the patients’ best interest that they are seen at a lithium bipolar patients with lithium induced renal side effects. They take part in a clinic that is equipped to identify the absence of (regular) Dutch research consortium of scientists working on the renal side effect of renal monitoring and detect insidious renal dysfunction lithium treatment. in a timely manner, and where staff has expert knowledge Author details about lithium-induced renal damage so that they can be 1 2 Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands. CWZ Hospital, optimally informed about the options available to them. Nijmegen, The Netherlands. Reinier van Arkel, ‘s-Hertogenbosch, The Nether- lands. Radboudumc, Nijmegen, The Netherlands. Our survey demonstrates that this is exactly what the patients who have to cope with a serious mood disorder Acknowledgements on a daily basis want and expect. No acknowledgment. Competing interests Conclusions No competing interest. • This is the first paper that focuses on the opinions of Availability of data and materials lithium patients who developed end stage renal dis- Data can be shared, please contact the corresponding author. ease. • Retrospectively, the treatment and monitoring of Consent for publication Patients gave consent for publication. lithium and the information process were inadequate in many cases. Ethics approval and consent to participate • We give suggestions on how to inform patients tak- The study was approved by the Reinier van Arkel ethical committee. ing lithium for their BD timely and adequately on the Funding course of renal function loss in the various stages of No funding. their treatment. Kerckhoffs et al. Int J Bipolar Disord (2018) 6:13 Page 7 of 7 Fraenkel L, McGraw S. Participation in medical decision making: the patients’ Publisher’s Note perspective. Med Decis Making. 2007;27(5):533–8. Springer Nature remains neutral with regard to jurisdictional claims in pub- Goodwin GM, Haddad PM, Ferrier IH, et al. Evidence-based guidelines for lished maps and institutional affiliations. treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. Received: 6 February 2018 Accepted: 21 March 2018 2016;30(6):495–553. Hajda M, Prasko J, Latalova K, et al. Unmet needs of bipolar disorder patients. Neuropsychiatr Dis Treat. 2016;12:1561–70. Lepkifker E, Sverdlik A, Iancu I, et al. Renal insufficiency in long-term lithium treatment. J Clin Psychiatry. 2004;65:850–6. References Miura T, Noma H, Furukawa TA, et al. Comparative efficacy and tolerability of Alguera-Lara V, Dowsey MM, Ride J, Kinder S, Castle D. Shared decision making pharmocological treatments in the maintenance treatment of bipolar in mental health: the importance for current clinical practice. Australas disorder: a systematic review and network meta-analysis. Lancet Psychia- Psychiatry. 2017;25(6):578–82. try. 2014;1(5):351–9. Bendz H, Schon S, Attman PO, et al. Renal failure occurs in chronic lithium Nielsen RE, Kessing LV, Nolen WA, Licht RW. Lithium and renal impairment: a treatment but is uncommon. Kidney Int. 2010;77:219–24. review on a still hot topic. Pharmacopsychiatry. 2018. https://doi.org/10.1 Cipriani A, Pretty H, Hawton K, Geddes JR. Lithium in the prevention of suicidal 055/s-0043-125393. behavior and all-cause mortality in patients with mood disorders: a sys- Oxman AD, Chalmers I, Sackett DL. A practical guide to informed consent to tematic review of randomized trials. Am J Psychiatry. 2005;162:1805–19. treatment. BMJ. 2001;323(7327):1464–6. Fisher A, et al. A qualitative exploration of clinician views and experiences Presne C, Fakhouri F, Noel LH, et al. Lithium-induced nephropathy: rate of of treatment decision-making in bipolar II disorder. Community Ment progression and prognostic factors. Kidney Int. 2003;64:585–92. Health J. 2017b;53(8):958–71. Verwijmeren D, Grootens KP. Shared decision making in pharmacotherapy Fisher A, Manicavasagar V, Sharpe L, et al. Qualitative exploration of patient decisions, perceived by patients with bipolar disorder. (under review). and family views and experiences of treatment decision-making in bipo- lar II disorder. J Mental Health. 2017a;27(1):66–79.

Journal

International Journal of Bipolar DisordersSpringer Journals

Published: Jun 2, 2018

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