The New Lithium Clinic

Neuropsychobiology 2010;62:17–26 DOI: 10.1159/000314306 Published online: May 7, 2010 The New Lithium Clinic Yamima Osher Yuly Bersudsky R.H. Belmaker Beer Sheva Mental Health Center, Ministry of Health and Ben Gurion University of the Negev, Beer Sheva, Israel Key Words Bipolar disorder ⴢ Lithium clinic ⴢ Treatment model ⴢ Psychotherapy Abstract Until the early 1950s, no effective pharmacological treatment existed for bipolar affective disorder. By the early 1960s, specialty clinics were being set up to dispense lithium carbonate to bipolar patients. By the late 1980s, a new body of knowledge was influencing the perception of bipolar disorder and how the disease should be treated. The authors’ lithium clinic from 1974 has grown and evolved from a lithium blood level monitoring model into a comprehensive care model with polypharmacy, psychoeducation, rehabilitation, cognitive therapy, social rhythm therapy, and employment counseling as well as a staff of 2 part-time psychiatrists and 1 clinical psychologist. This service delivery model may benefit both treatment and research in bipolar disorder. The evolution of psychopharmacological and psychosocial knowledge in treating bipolar illness has been integrated into our clinic. Case vignettes are presented to illustrate these points. The comparative cost of this model is discussed. Copyright © 2010 S. Karger AG, Basel © 2010 S. Karger AG, Basel 0302–282X/10/0621–0017$26.00/0 Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Accessible online at: www.karger.com/nps Introduction: Historical Background Report of the prophylactic efficacy of lithium caused excitement and a flurry of research into this simple but powerful ion [1]. By the early 1960s, specialty clinics were being set up explicitly to dispense the drug. One of the first of these ‘lithium clinics’ was established in New York by Fieve [2]. Kerry in Sheffield, UK [3] and a group of private practitioners in Normal, Ill., USA [4] published early reports of similar ‘lithium clinics’. In the late 1970s, the name ‘lithium clinic’ continued to be popular [5]. These early clinics functioned in a way designed to maximize efficiency, especially regarding physician’s hours, based on the perception that the blood level of lithium was the main target of intervention. Patients were often seen by a nurse, individually or in a group, or by paramedical personnel who filled out rating scales. Blood levels were taken, and typically the physician was called in ‘only if the patient requires a change in dosage, is experiencing mood change, or shows possible symptoms of toxicity’ [2]. In one clinic, if the patient was unable to attend, blood samples were simply sent in by the local health authority [3]. As late as the 1990s, clinicians who had worked with lithium clinics could write how their experiences had ‘impressed upon us the potency and effectiveness of lithium, and its ability to transform patients’ lives from disastrous to manageable and normal’ [6]. Yamima Osher Ministry of Health, Beer Sheva Mental Health Center, Faculty of Health Sciences Ben Gurion University of the Negev PO Box 4600, Beer Sheva 84170 (Israel) Tel. +972 8 640 1519, Fax +972 8 640 1621, E-Mail yamy @ bgu.ac.il A different model developed in Berlin in the early 1980s, where the lithium clinic annually treated about 100 mood disorder patients [7]. In this clinic, which saw each patient an average of 8 times per year, the patient was seen by a psychiatrist at each visit, not only by a nurse or social worker. This multidisciplinary approach emphasized talking to the patients about their problems, not only checking compliance and filling out new prescriptions. The social worker assisted the patient in finding employment and living arrangements, and intervened in crises [7]. By the late 1980s, a growing body of knowledge was changing the perception of bipolar disorder overall. The authors’ lithium clinic began in 1974 in Jerusalem, moved to Beer Sheva in 1985, employed a psychologist in 1990 and a second psychiatrist in 2000. From 1974 to 1985, one of the authors (R.H.B.) had an EEL flame photometer [8] in his office and performed serum lithium determinations himself while patients waited. At present, the clinic is a regional specialty clinic serving approximately 180 bipolar I patients. While the catchment area of our clinic includes 500,000 residents, patients also have access to private care or to a psychiatry clinic in the general medical hospital. They come to our University Bipolar Clinic voluntarily. Usually referral is at discharge from one of the inpatient wards (the only inpatient service in our catchment area) and for this reason our clinic is limited to bipolar I patients. Patients are aware of the advantage of continuity of care that our clinic offers and that, on the other hand, the likelihood exists of being approached for participation in research trials. Some complain of long waiting times or the lack of waiting room privacy. Solutions to this last issue have not been found consistent with our large patient volume and cost considerations (see below). This paper will describe the evolution of both psychopharmacological and psychosocial approaches to treating bipolar illness in our clinic, and how these changes have been integrated into clinical practice. Case vignettes from our clinic are presented to illustrate particular points and the cost of this model will be discussed. Pharmacotherapy New developments in the psychopharmacology of bipolar disorder have been reviewed extensively in recent years [9, 10]. It is increasingly recognized that the average bipolar patient takes several medications with the goal of reducing to a minimum the number of manic and depres18 Neuropsychobiology 2010;62:17–26 sive recurrences, even though monotherapy trials versus placebo show effectiveness for each of the compounds [10, 11]. The first compound to be reported as effective in addition to lithium in the prophylaxis of bipolar disorder was carbamazepine by Okuma et al. [12] in Japan, although the work was greatly extended and given scientific impact in both basic and clinical studies by Post et al. [13]. Carbamazepine was added to the therapeutic armamentarium in our clinic in the early 1980s [14]. At a meeting in Basel in 1989 relating to the possible development of oxcarbazepine, internal documents of Ciba Geigy, which was then the exclusive supplier of carbamazepine, showed that worldwide off-label sales of carbamazepine for bipolar disorder represented about half of worldwide sales of the anticonvulsant. Few controlled studies were done, however, and only recently was a long-acting carbamazepine preparation FDA approved for bipolar disorder. Valproic acid had similarly been reported to be effective in bipolar disorder in Europe by Emrich et al. [15], but the major impact and acceptance of this medicine came after controlled American trials by Bowden et al. [16]. Valproate began to be widely used in our clinic by the late 1990s. The divalproex sodium preparation was never used, only generic valproic acid. More recently, lamotrigine was FDA approved for bipolar disorder and its use has been reviewed [17]. While the fact that several anticonvulsants are effective in bipolar disorder would suggest a relationship between seizure disorder and bipolar disorder, no pathophysiological evidence has been proven to support this hypothesis. It would appear that anticonvulsants that act on the sodium channel are usually effective in bipolar disorder, whereas anticonvulsants such as phenobarbital or clonazepam that act on the benzodiazepine receptor are ineffective in bipolar disorder [18, 19]. Sometimes phenytoin was used as a counterexample of a good anticonvulsant that is not effective in bipolar disorders; however, our own studies suggest that phenytoin may indeed be effective [20]. Topiramate was studied for bipolar disorder but failed in large clinical trials. This failure may have been due to the large number of antidepressant-induced manias in those studies that led to a corresponding high response rate of the placebo group. The fact that topiramate is not approved as an antibipolar drug does not prove the opposite, i.e., that it is not an antibipolar drug. This distinction is very important in deciding what to do for a patient who has not responded to any other treatment and topiramate has been occasionally useful. Osher/Bersudsky/Belmaker Our concept of the specificity of pharmacological treatment of bipolar disorder is illustrated in figure 1. It would be scientifically elegant if we could divide bipolar patients into (1) those that are lithium responsive and unresponsive to anticonvulsants and (2) those that are lithium unresponsive and responsive to anticonvulsants. If this were true, it would be useful in further genetic studies of bipolar disorder as well as in pathophysiology. However, this is not the case clinically: we had patients who were responsive to both lithium and anticonvulsants as well as patients who were unresponsive to both lithium and to anticonvulsants. These clinical facts become evident when a patient must stop lithium because of side effects and go over to an anticonvulsant and vice versa. There clearly are some patients who are uniquely responsive to lithium but many quite typical bipolar patients who had to stop lithium have done equally well on valproate or carbamazepine. Many atypical antipsychotics have been shown to be effective in several phases of bipolar disorder and are recommended in guidelines to this effect [21], particularly quetiapine, ziprasidone, olanzapine, risperidone and aripiprazole. However, the novelty of this finding is reduced by a careful search of the literature of the 1960s and 1970s where studies found that first-generation antipsychotics such as flupenthixol were prophylactic in bipolar disorder [22–25] as well as of course antimanic [26]. The early studies of antidepressants [27] found that chlorpromazine and other typical antipsychotics were equal to imipramine in depression. Thus, it is not clear if antibipolar prophylactic efficacy is unique to the new atypicals or has always been a property of dopamine D2-blocking compounds. The sensitivity of bipolar patients to the weight gain and diabetogenic side effects of the new atypicals cannot be ignored. Many patients in our clinic are maintained on a combination of lithium and a typical antipsychotic such as perphenazine. However, others have done well on olanzapine, risperidone, ziprasidone and more recently quetiapine. Our impression with the antipsychotic medications has been similar to our experience with the anticonvulsant treatments: individual sensitivity and individual side effect acceptability seem to be more important than whether a particular compound is FDA approved for a particular indication. The advantage of long-term treatment of patients is that their individual optimal treatment can often be discovered in a manner that adds to evidence-based medicine. Evidence-based medicine in our clinic is no substitute for individualized care by a physician who knows the patient’s baseline as well as the patient’s response to medicine cessation that inevitably occurs at least several times over the long-term course of bipolar disorder. Bipolar depression is a source of less morbidity in our clinic than in reports from the USA or Europe, and we found that our patients, all bipolar I, have 3 manias for every depression [28]. This could be due to ethnic, genetic, or climactic factors or to the selection of patients, since our referrals come from hospital admissions that are almost always manic. Our clinical experience matches the recent American study [29] claiming that SSRIs are rarely useful in bipolar depression [30], but also the European experience that mixed noradrenergic-serotonergic antidepressants can alleviate bipolar depression [31]. We frequently see antidepressant-induced mania and try to treat mild-moderate bipolar depression with omega-3 fatty acids [32], folic acid [33], exercise [34, 35] and psychosocial intervention [36] to reduce mania risk. The long-term follow-up in our clinic has led us to value Angst’s distinction between Md (worse and more frequent manias than depressions), mD (worse and more frequent depressions than manias) and MD (equal depressions and manias) patients [37]. Antidepressants are clearly less risky in patients whose past manias have been New Lithium Clinic Neuropsychobiology 2010;62:17–26 Lithium responders Antipsychotic responders A B C Anticonvulsant responders Fig. 1. Contemporary psychopharmacology of bipolar disorder. The enclosed areas represent ‘sets’ of patients successfully treatable prophylactically with each group of antibipolar drugs. A = Those who have done well with either lithium or an anticonvulsant or antipsychotics; B = those who have done well with an anticonvulsant but did not respond to antipsychotic or to lithium; C = those who achieve euthymia on lithium or an anticonvulsant but not on antipsychotics. 19 Start lithium 1,800 mg Add imipramine 75 mg 6 Severe 4 Mania Moderate 2 Mild Fig. 2. Imipramine prophylaxis of residual depression in a lithium-treated bipolar patient. This patient’s history is convincing to us of the utility of imipramine addition to lithium prophylaxis, and the lack of manic relapse in this patient. Longitudinal data are often more important for specific patients in our clinic than knowledge of the latest randomized trial of a large number of unselected patients. Depression Mild –2 Moderate –4 Severe –6 1 2 3 4 1992 mild than in those whose past manias were life-threatening. Some mD patients require chronic maintenance with mood stabilizers plus tricyclics or MAOI. As Prien et al. [38] and others have shown, such a strategy risks increased manic relapses in the general bipolar population but careful history and close acquaintance over time can minimize this risk. The cost-benefit ratio for specific patients is highly favorable (for instance, see the patient illustrated in figure 2). Few patients in our clinic have participated in prophylactic controlled trials because our patients are well informed and have usually seen monotherapy versus placebo as too risky. Our patients have been more likely to participate, during relapse and inpatient interludes, in acute controlled trials of add-on drugs in mania [26, 39]. The largest outpatient prophylactic clinical study done in our clinic was an add-on study of phenytoin in addition to the patients’ ongoing antibipolar regime [20]. Disability and Vocational Rehabilitation The classic Kraepelinian diagnosis of bipolar disorder included the concept of restitutio in integrum, i.e. that patients were restored to their original normal personality and functioning between episodes. While this is true 20 Neuropsychobiology 2010;62:17–26 1 2 1995 1 2 3 4 5 6 7 8 9 10 1 2 2000 2008 for perhaps a third of bipolar patients, long-term followup studies have shown that bipolar patients suffer from residual symptoms 30–50% of the time [40, 41], and that relapse occurs at a very high rate [40]. Up to two thirds of bipolar patients show significant decline in overall functioning (social adjustment and vocational activity) [42]. Total disability is not uncommon in bipolar disorder, and partial and/or temporary disability is considerably more common. A German study [43] found that half of 61 consecutive bipolar inpatients had been granted disability payments by their mid-forties; approximately 15% of the STEP-BD (Systematic Treatment Enhancement Program for Bipolar Disorder) sample reported their occupational status as ‘disabled’ [44]. Even when bipolar patients are virtually symptom free, their psychosocial functioning is still significantly below that of a healthy comparison group [45]. Divorce and marital separation are 2–3 times more likely than among the general population in the US [44, 46]. It is increasingly clear that the disorder is accompanied by neuropsychological [47] and cognitive [48] impairment even in the euthymic state. Euthymic bipolar patients show neuropsychological functioning which is superior to that of schizophrenic patients, but inferior to healthy comparison subjects [49]; problems are found most consistently in attention, memory, and executive function [50]. There is evidence that these cognitive defOsher/Bersudsky/Belmaker icits are related to poorer overall functional outcome, particularly the impairments in verbal memory and executive function [51], and that these deficits may be linked specifically to poorer occupational functioning [52]. This changing picture has influenced our approach to vocational rehabilitation, leading in many cases to a strategy of more modest goals. Thirty and even 20 years ago, we communicated to patients and families the expectation of full return to employment or studies within 3–6 months after hospital discharge from an acute affective episode. Now experience suggests an incremental approach to return to work, longer timetables for academic or vocational study programs, and more attention to risk factors such as irregular work hours or high-stress positions in the choosing of employment. We sometimes find ourselves having to interpret this message to families of patients, when their well-intentioned efforts to encourage the patient to do more and more are actually endangering the patient’s well-being. While we continue to encourage patients to reach optimal levels of functioning in as many areas as possible, we have come to see that often, ‘less is more’. More modest levels of achievement and functioning which can be sustained over time are preferable to overestimating abilities, over-reaching and exacerbating or even inducing recurrent affective episodes. Psychological Treatment Special emphasis is placed on setting and reaching one goal at a time, with adequate time between important milestones such as marriage, childbirth, commencing or completing studies, changing jobs, and moves to a new location. Bipolar disorder is clearly a biologically based illness with high heritability. A few decades ago, the expectation seemed to be that good blood levels of lithium alone would normalize the bipolar patient [53]. In early years, the lithium ion was thought to be a specific treatment for core bipolar disorder [54]. There is now considerable evidence that psychological or psychosocial interventions also have a significant impact on the course of the disease [55]. Research demonstrating the negative impact of high-expressed emotion in families on the relapse rates of schizophrenic patients [56] was soon found to be true also for affective disorders [57–59]. Several modes of psychotherapy have demonstrated usefulness as add-ons to treatment as usual in the management of bipolar disorder [60]. Interpersonal and social rhythm therapy focuses on personal problems such as grief, conflict resolution, and ineffective behaviors. It stresses the importance of maintaining regular schedules of sleep/wake, socializing, exercise, and work. This approach showed efficacy in a 2-year follow-up study [61]. Cognitive-behavioral therapy around medication compliance and depressive symptomology improved time to relapse, time well and social functioning over 1and 2-year follow-up periods [62, 63]. See Miklowitz [36] for a comprehensive review of the evidence to date. Psychoeducation with caregivers and family members of bipolar patients has also been shown to reduce risk of additional episodes [64]. We have made a concerted effort to include family members in the treatment of our clinic participants. Family members are involved in the ongoing follow-up treatment, and we endeavor to help them become active and informed members of the treatment team. A small booklet in Hebrew is given out to patients and families. This booklet, entitled Bipolar Disorder (Manic-Depression) [65], is one of a series which includes up-to-date information on a variety of medical and psychiatric disorders, presented in a well-organized and accessible manner, in clear everyday language. Additional recommended resources for English speakers range from a brief outline which succinctly summarizes main points describing the disorder and its management [66] to more comprehensive books. The Bipolar Disorder Survival Guide [66] is addressed directly to the bipolar patient, and conducts a sort of dialogue with the patient, addressing common fears, concerns and misunderstandings, imparting information together with a strong emphasis on selfhelp, self-care, and self-monitoring of mood states. The book includes many case vignettes, a section on additional resources and a complete list of references. A compre- New Lithium Clinic Neuropsychobiology 2010;62:17–26 R.Z. is a 37-year-old single woman who is intelligent and artistic. She had little trouble finding work, but after performing successfully in a part-time capacity, she enlarged her workload to full time, and within a short time succumbed to a psychotic episode which entailed the loss of the job and an extended period of recovery. Only after she was able to see the pattern, and after receiving support for the idea that functioning well part-time was an acceptable outcome, did she limit her work hours and achieve a relatively long and stable remission. This also allowed the long delayed development of a satisfying romantic relationship. A second patient (R.W.), a social worker, experienced severe episodes while trying to retain various full-time, high-stress positions, but has now been able to remain healthy while working in her profession but at a part time low-stress position. A third patient (D.R.) suffered repeated exacerbations every time she attempted to return to work in her profession (nursing), but has been able to remain stable while working part time as a cosmetician. Patients have successfully completed academic degrees often only after accepting the need to spread the studies out over a longer than usual period of time, or accepting a less demanding course of study (such as a terminal MA, without thesis, as opposed to an MA with thesis). 21 Table 1. Prescribing patterns in the Beer Sheva Lithium Clinic (1993 and 2008) a Percentage of patients prescribed medications of each class 1993 (n = 54) 2008 (n = 155) Lithium Anticonvulsant Typical Atypical Antiantiantideprespsychotic psychotic sant 96 62 39 15 17 27 – 47 11 9 b Percentage of patients receiving monotherapy or polypharmacy (2, 3, or 4 medications) 1993 (n = 54) 2008 (n = 155) Monotherapy 2 Medications 3 Medications 4 Medications 46 48 44 40 7 11 2 1 hensive and user-friendly contribution to this literature is Bipolar Disorder for Dummies [67]. Deceptively lighthearted, with cartoons and the breezy contemporary style for which the ‘For Dummies’ series is noted, this book is actually a thorough and well-researched compendium of information and practical tips. The book is especially notable for its discussion of an ‘emergency plan’, a step-bystep guide to preparing for a possible crisis in the future. This book also includes a chapter on pediatric bipolar disorder, a section directed to friends and relatives who assist the patient, and a useful glossary of terms which can help improve patient-physician communication. Schou’s [68] original booklet for patients and families is out of date. We noted a special difficulty in working with parents of young adult bipolar patients. Whereas the patients, in many cases, had previously achieved a significant level of independence, the onset or exacerbation of the disorder resulted in a return to dependent or semi-dependent status – difficult for both patient and families to navigate. A support group for parents of adult bipolar patients was established, with the psychologist and a senior social worker as co-therapists. Over the course of several years, the group evolved from a more psychoeducational framework to one of mutual support; once the co-therapists were unable to continue, the group continued to meet, informally, without professional input. A. is an unmarried man in his early 30s. Ill since his high school days but undiagnosed until his late 20s, A. was overly dependent on his parents and was seen as a failure by his younger sisters. In a series of family meetings utilizing reframing, struc- 22 Neuropsychobiology 2010;62:17–26 tural interventions, goal setting and problem-solving techniques, expressed emotion on the part of the parents and the sisters was reduced and the patient was able to accept their appropriate help. He attained gradual improvement in functioning in a variety of roles ranging from housekeeping to gainful employment. The improvement in the family atmosphere facilitated the gradual movement of the patient towards a more appropriate level of independence, and for the first time, he was able to move out of the family home into his own apartment. Later, during three acute manic exacerbations, the high level of cooperation within the family and also between the family and the clinic staff enabled hospitalization to be avoided without endangering the patient or the family. The Beer Sheva Mental Health Center Bipolar Disorder Clinic About 10 years ago, the sign outside our clinic was changed from ‘Lithium Clinic’ to ‘Bipolar Disorder Clinic’ at around the time that only about half the patients were receiving lithium treatment (table 1). Each psychiatrist holds clinic 1 day per week from 9:00 a.m. to 3:00 p.m. Euthymic patients are generally invited to the clinic monthly; in rare emergencies, patients can be seen as often as several times per week. Patients are scheduled at 10- to 15-min intervals, and the delays which develop naturally over the day lead to an informal ongoing support group forming in the waiting area. The patient is seen by a psychiatrist together with the psychologist. During the appointment attention is given to overall assessment, to medication issues (dosage, side effects), and blood is drawn for levels of lithium or valproate or carbamazapine, or white blood cell count for clozapine patients, as required. The clinic visit is a prime opportunity for psychoeducation regarding the illness and its treatment. Topics include the nature of the disorder, symptoms, triggers and risk factors, medications and side effects, early detection of episodes, stress management, and lifestyle changes which can promote health and stability [69]. Family members often accompany the patient, and this is an important opportunity to recruit them to the treatment team, to provide psychoeducation and support, and to establish a rapport which can be critical in times of exacerbation. All patients, and their main supporters, are provided with the direct phone number of the psychologist. Scheduling and most routine inquiries are handled by the psychologist, who will contact the treating psychiatrist outside of clinic days only if necessary. The close involvement of the psychologist in the ongoing care of all patients generally allows the patients to feel that they have direct, continual access to a signifOsher/Bersudsky/Belmaker icant caregiver and at the same time demands on the physician’s time are reduced. The clinic appointment is a chance to hear about life events, stressors, conflicts, or other psychosocial problems which may require our intervention. Often time is insufficient and separate appointments are set up with the psychologist on nonclinic days. Some patients see the psychologist on a regular basis, for ongoing therapy; other patients and many families consult with her on an ‘as needed’ basis for interventions of varying length and intensity. The psychologist coordinates most rehabilitation programs and also prepares most entitlement forms for disability insurance, driving licenses and forensic evaluations. This strengthens the therapeutic alliance with the patient and enhances compliance with medication and clinic visits. The Bipolar Clinic in its present form is conducive to both research and teaching opportunities. Clinic patients are well known to the staff and the average patient has been in treatment with the same staff for 10 years. Determinations of euthymic status or residual symptoms can be made with a high degree of confidence by comparison with a known baseline. Patients are used to blood being taken for determination of blood levels and very seldom object to small additional amounts of blood being drawn for research purposes (after obtaining written consent). Many important studies have resulted [70–72]. The clinic is often host to student groups (medical, nursing, and neuropsychology students) and provides a unique opportunity for students to see not the acute pathology of the inpatient wards but psychiatric patients who seem ‘normal’ and healthy despite their ongoing battle with a serious illness. The Cost of the New Model for Bipolar Service Delivery Pharmacological treatment of bipolar disorder is inadequate by itself; as Huxley and Baldessarini [42] conclude in their recent review, interpersonal, cognitive-behavioral, and psychoeducational interventions with bipolar patients can reduce risk of relapse, hospitalizations, and symptom severity as well as improve social and vocational outcomes. The addition of cognitive therapy to standard pharmacological treatment was found to be cost-effective as well as clinically superior [73], as the direct costs of the additional therapy were offset by reductions in other types of service usage. A collaborative care model utilizing a nurse care coordinator rather than a psyNew Lithium Clinic Table 2. Economics of the new lithium clinic model Expenses per month – salaries Psychiatrist (R.H.B. and Y.B.), 1/5 position each, !2 (2 psychiatrists, 1 day a week for each) Clinical psychologist (Y.O.), 3/4 position ⬃10,000 NIS ⬃10,000 NIS Total ⬃20,000 NIS Income per month (from the Ministry of Health list of charges for services) Follow-up medication clinic visits – psychiatrist plus psychologist (charge for psychiatrist time only) 160 visits/month ! 94 NIS/visit ⬃15,000 NIS Individual psychotherapy – psychologist 24 visits/month ! 200 NIS/visit ⬃5,000 NIS Family and couples counseling – psychologist 16 visits/month ! 235 NIS/visit ⬃4,000 NIS Psychosocial interventions and follow-up – psychologist 40 visits/month ! 108 NIS/visit ⬃4,000 NIS Total ⬃28,000 NIS The above model does not include laboratory costs, office space rent, computer and chart services and other overhead expenses. But it suggests that our model is within the guideline reimbursements projected for mental health services as part of the extension of National Health Insurance in Israel to include mental health on ‘parity’ basis with general medicine within the 4 national HMOs. chologist [74] has been shown to improve long-term clinical and functional outcomes in both a severely ill, frequently hospitalized cohort of bipolar patients [75] as well as in a less severely ill health maintenance organization sample [76]. The model was associated with a modest increase in cost as compared to treatment as usual for the HMO group [76]. For the more severely ill group, small increases in outpatient costs were more than offset by reductions in spending on inpatient care [75]. Under the proposed ‘Reform’ of Israeli mental health services, psychiatric hospitals and outpatient services will be reimbursed for services to members by the Health Maintenance Organizations which provide coverage to all citizens. Within the parameters of the current simulation figures in use, a very basic modeling of our clinic shows a favorable ratio of costs (salary) to income, as can be seen in table 2. Salary costs are computed based on total cost to employer, not only gross salary. Amounts shown are in New Israeli shekels (NIS); at current rates of exchange, 1 USD = 4 NIS (approximately). Neuropsychobiology 2010;62:17–26 23 Conclusion Over the last 35 years, our Lithium Clinic ] Bipolar Clinic has evolved. Bipolar patients often feel out of place in clinics designed for injectable or oral medication follow-up for schizophrenic patients. On the other hand, general psychiatric clinic practice may not provide specialized pharmacologic knowledge, availability of therapeutic drug level monitoring, rapid response to acute manic emergencies [30] and psychological services by a psychologist expert in mood swings. Changes over the last 35 years have not been only, or even primarily, exciting new pharmacologic treatments that help many but not all patients. Prognosis has been revised to include possible deterioration as well as drug nonresponse. Patients and families sometimes must hear this prognosis in an empathic way at an appropriate time. Psychoeducation and psychotherapy have been integrated in a way that might surprise early hopes for lithium as psychiatry’s ‘magic bullet’ [77]. Acknowledgment Thanks go to Eli Lepkifker who founded the first lithium clinic in Israel. References 1 Schou M: Lithium in psychiatric therapy. Stock-taking after ten years. Psychopharmacologia 1959;1:65–78. 2 Fieve RR: The lithium clinic: a new model for the delivery of psychiatric services. Am J Psychiatry 1975;132:1018–1022. 3 Kerry RJ: A special lithium clinic. Dis Nerv Syst 1969;30:490–492. 4 Bey DR, Chapman RE, Tornquist KL: A lithium clinic. 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