Assessment of lithium-related knowledge and attitudes among patients with bipolar disorder on long-term lithium maintenance treatment.

BACKGROUND: Gaps in lithium-related knowledge among bipolar disorder (BD) patients on lithium prophylaxis may pose safety concerns and could adversely influence attitudes to lithium.
OBJECTIVE: To assess the lithium-related knowledge and attitudes among patients with BD.
MATERIALS AND METHODS: This was a cross-sectional, observational study assessing euthymic, adult outpatients with BD on lithium prophylaxis (≥1 year) using a semi-structured pro forma, lithium questionnaire for knowledge, lithium attitude questionnaire (LAQ), and medication adherence rating scale (MARS).
RESULTS: Descriptive analysis revealed several deficits in knowledge, including lack of critical safety information or need for periodic blood tests. Lower knowledge group had significantly more negative attitudes. Favorable attitude toward lithium (lower LAQ score) was significantly associated with the number of psychiatric follow-ups in the last year and MARS score.
CONCLUSION: There were critical deficits in lithium-related knowledge among the patients. Lower lithium knowledge was associated with negative lithium attitudes. Educative interventions should be delivered periodically to regular lithium users. Copyright:

INTRODUCTION

In spite of advent of newer agents, lithium is still preferred in clinical practice for the management of bipolar disorder (BD) and is among the first-line maintenance agents.[1] However, lithium-related knowledge might be “dangerously little” or “limited” even among regular attendees on prescribed prophylactic treatment from specialized clinics.[23] About one-fourth of patients on regular lithium believed that it was being prescribed because they were lithium deficient. Moreover, even adherent patients might still show surprisingly low levels of lithium knowledge,[45] putting them at a greater risk for toxicity. Apart from safety and efficacy concerns, the deficits in knowledge negatively influence the attitudes toward medication.[67]

However, till date, no published work from India has specifically focused on lithium-related attitudes or lithium knowledge. A PubMed-based electronic search (using key terms) supplemented with MedInd and Google Scholar returned only one related paper assessing medication adherence in a BD sample on various medications, wherein drug attitudes were assessed in relation to adherence.[8]

A previous paper[9] from our larger nonfunded project had focused on lithium adherence and its clinical predictors, highlighting that adherence remains far from ideal in an exclusive lithium-maintained cohort with BD.[9] The present paper, also a part of that nonfunded project, primarily focused on providing descriptive account of lithium-related knowledge and attitudes.

MATERIALS AND METHODS

Study settings and participants

This cross-sectional, observational study was conducted at a tertiary care teaching hospital in North India between April 2018 and January 2019. Institutional ethics committee clearance was obtained before initiation of the study. Written informed consent was taken from all participants.

Adult outpatients with BD diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders-5 criteria,[10] on lithium prophylaxis for at least 1 year or more, and in clinical remission for at least past month or more (as per history and records) were approached for inclusion in the study. Patients with a comorbid major psychiatric disorder other than alcohol/tobacco dependence were excluded. The clinical care of the patients was continued as usual.

Assessment tools

A semi-structured pro forma was used to gather relevant sociodemographic and clinical characteristics of the participants. The information was obtained from all available sources of information, including treatment records

Lithium questionnaire (LQ) is a semi-structured questionnaire with 13 questions exploring lithium-related knowledge in a Yes/No format and empty spaces next to each item to seek elaboration from the respondent, as required.[4] The maximum LQ score of 13 is possible, with a score of one per item, although it has been primarily employed for descriptive purposes. The theme of questions in LQ broadly represents those explored in the lithium knowledge test (LKT) developed from Peet and Harvey's work,[11] which has a more structured format with seven multiple-choice questions. In the absence of any recent or valid scale to assess for lithium-related knowledge, we have used a questionnaire approach based on Lee et al.,[4] to facilitate comparisons and to provide descriptive information about deficits in lithium-related knowledge

Lithium attitude questionnaire (LAQ) comprises 19 self-rated items (Yes/No format) assessing individual attitudes toward prophylactic lithium treatment.[12] It comprises seven subscale scores assessing attitude toward different aspects associated with lithium treatment. LAQ has a possible score range of 0–19, with higher scores indicating greater degree of negative attitudes toward lithium prophylaxis.[12] LAQ was found to be the only valid and reliable tool for the assessment of lithium attitudes[67]

Medication adherence rating scale (MARS) is a brief, valid, and reliable instrument,[13] pertaining to adherence behaviors, with higher scores indicative of better adherence.

Statistical analysis was done using Statistical Package for the Social Sciences version 23.0 (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp). A two-tailed P < 0.05 was considered statistically significant.

RESULTS

A total of 84 participants with BD were recruited of which five had to be excluded from final analysis due to missing key data. The final study sample comprised of 79 participants.

Table 1 shows the sociodemographic and clinical profile of the study sample and also describes the lithium attitudes as assessed on LAQ.

Table 1

Sociodemographic, clinical profile and lithium attitudes of the study sample (n=79)

Variable	Mean±SD or n (%)
Age (years)	35.71±10.76
Gender
Male	48 (60.8)
Female	31 (39.2)
Education
Illiterate	3 (3.8)
<10th standard	14 (17.7)
≥10th standard and below graduate	33 (41.8)
Graduate or above	29 (36.7)
Socioeconomic status
Lower	8 (10.1)
Lower middle	39 (49.4)
Upper middle	30 (38.0)
Upper	2 (2.5)
Marital status
Never married	28 (35.5)
Married	46 (58.2)
Separated/divorced	5 (6.3)
Age at onset (years)	25.35±6.92
Duration of illness (months)	123.87±96.88, median= 84 (IQR: 44-192)
Duration of lithium therapy (months)	50.96±60.06, median= 26 (IQR: 15-66)
Number of visits with psychiatrist in the past year	4.44±3.37, median= 4 (IQR: 3-5)
Lithium monotherapy as prophylaxisa
Yes	38 (48.7)
No	40 (51.3)
Lithium prescription in the first-degree relativea
Yes	7 (9.0)
No	71 (91.0)
Prior psychiatric hospitalization
Yes	42 (53.2)
No	37 (46.8)
Comorbid medical disordera
Yes	15 (19.2)
No	73 (80.8)
LAQ-total score (0-19)	7.78±4.55
LAQ-1:Opposed to continuing lithium treatment regimen (0-4)	1.73±1.21
LAQ-2:Denial of therapeutic effectiveness of lithium (0-2)	0.41±0.76
LAQ-3: Concern about side effects (0-2)	0.89±0.73
LAQ-4: Difficulty in maintaining pill taking routine (0-4)	1.53±1.34
LAQ-5: Denial of illness severity (0-3)	1.00±1.06
LAQ-6: Negative subcultural attitudes toward drug treatment (0-3)	1.43±0.98
LAQ-7: Dissatisfaction with factual knowledge of lithium (0-1)	0.80±0.40

aMissing data for one participant. IQR – Interquartile range; LAQ: Lithium attitude questionnaire and its seven subscales (LAQ 1–LAQ 7); SD – Standard deviation

Table 2 shows the item-wise responses on the LQ pertaining to lithium knowledge.

Table 2

Participants’ responses for lithium-related knowledge (n=79)

LQ: Knowledge questions*	Responses, n (%)
Do you know the name of the medication you have been taking?
Yes	61 (77.2)
No	18 (22.8)
Do you know why you are taking lithium? (drug name was told after Q1)
Yes	55 (69.6)
No	24 (30.4)
What is lithium used for?#
Tranquillizer (to reduce anxiety or mental stress)	32 (40.5)
Hypnotic (to promote or produce sleep)	22 (27.8)
Mood stabilizer (stabilizes mood)	34 (43.0)
Nutritional supplement or tonic for mind	32 (40.5)
None of them	1 (1.3)
Don’t know	7 (8.9)
Do you know what proportion of patients benefit from lithium?
Yes	11 (13.9)
No	68 (86.1)
Do you think you require periodic tests of serum lithium level?
Yes	51 (64.6)
No	28 (35.4)
Is a stable serum lithium level required for its effectiveness?
Yes	53 (67.1)
No	26 (32.9)
Are there any other blood tests you periodically require?
Yes	27 (34.2)
No	52 (65.8)
Do you know the common side effects of lithium?
Yes	28 (35.4)
No	51 (64.6)
Do you know the warning signs of lithium toxicity?
Yes	25 (31.6)
No	54 (68.4)
Are there dietary or any other precautions to take while on lithium?
Yes	29 (36.7)
No	50 (63.3)
Do you tell other doctors about your lithium treatment when you visit them?
Yes	38 (48.1)
No	41 (51.9)
Do you think lithium should be stopped during pregnancy?
Yes	66 (83.5)
No	13 (16.5)
Do you think you may have to take lithium for several years?
Yes	50 (63.3)
No	29 (36.7)

*Based on lithium questionnaire as described by Lee et al. (1992), the median score of sample was 7 (IQR: 4-9), with a score of one awarded for each correct response (0-13); #Total over 100% as multiple options chosen on Q3. IQR – Interquartile range

To assess the relationship of lithium-related knowledge to lithium attitudes, the study sample was divided (based on statistical median cutoff of 7 on LQ) into low (LQ <7) and high (LQ ≥7) lithium knowledge groups. The LAQ score was compared across patients with a low versus high lithium knowledge. Those in low knowledge group had a significantly higher mean LAQ score (9.92 ± 4.669) compared to high knowledge (5.90 ± 3.53) group (U = 377.50; P < 0.01), suggestive of more negative attitudes. The MARS score was significantly lower in low knowledge group compared to high knowledge group (5.77 ± 3.02 vs. 7.95 ± 2.20; U = 404.50; P < 0.01).

To assess the relationship of lithium attitudes to various clinical variables, Spearman correlation was used, which revealed a statistically significant negative correlation of LAQ total with the number of visits with psychiatrist in the past year (rs= −0.37; P < 0.01) and MARS score (rs= −0.73; P < 0.01). No significant relationship was observed with age, gender, education, marital status, illness duration and duration of lithium, lithium prescription in the first-degree relative, presence of comorbid medical disorder, or past psychiatric hospitalization.

DISCUSSION

The findings from this paper are relevant for lithium-maintained adult outpatients with BD. The study sample was on long-term lithium (median: 26 months) with a median of four outpatient visits over the last year, a long-standing BD (median: 84 months), with adequate representation from both genders, and largely literate patients.

One of the first observations includes a remarkable proportion with major deficiencies in lithium-related knowledge, including a lack of critical safety information. About two-thirds did not know about specific warning signs of lithium toxicity (68.4%) or any special precautions on lithium (63.3%), and half of them did not report being on lithium to other doctors while seeking consultation (51.9%). This is further complicated by the fact that one in three was unaware of the need for periodic serum level estimations (34.2%).

When compared to few previous international studies, findings were broadly similar. In a highly compliant lithium clinic sample, one-third of knowledge questions on an average were not answered.[3] In another study, 30% did not know why blood was taken, in spite of them undergoing periodic tests.[5] A high hazard score, derived from LKT, was reported.[5]

Interestingly, about one-fifth (22.8%) of the sample could not name their medication (any generic or commercial names of lithium were acceptable). Two previous studies, by Lee et al. and de Souza et al.,[414] asked this exact question, with 20% and 38% unable to name it, respectively. Majority was unaware of the “mood-stabilizing properties” of lithium, believing it to be a sedative, or tranquilizer, etc., Such patients might discontinue it without understanding the implications thereof. An study conducted among Chinese BD outpatients reported a similar pattern and frequency of deficits in lithium knowledge, with some differences, such as 78% knew of mood-stabilizing properties (as opposed to 43% in the present study).[4]

Not surprisingly, the responses on “pregnancy question” had an overwhelming majority (83.5%) favoring to stop lithium during pregnancy. In the elaboration section, however, they could not provide any specific information on teratogenic risks. In clinical practice, stopping of lithium is not always a straightforward decision, with individual case considerations in mind.[115] Finally, one in three (36.7%) did not think that they need to take lithium for several years. Efforts must be made to prevent self-initiated lithium discontinuations in such patients.

Another main observation is the presence of significantly negative attitudes for lithium, relative to two earlier studies, also using LAQ.[67] The current sample reflects a median score of 6 (interquartile range[IQR] 4–10) on LAQ (score range 0–19), while a similar study from Brazil found a much lower mean score (3.5 ± 3.2).[7] Another study from the United Kingdom (UK) reported a median LAQ score of 2 (IQR 1–5).[6] Similar to that observed in the present study, available studies have consensus that positive lithium attitudes are associated with better adherence[6] and a greater number of visits/contacts with psychiatrists over the last year.[7816] The lower knowledge group had a significantly more negative attitude to lithium treatment and poorer adherence, broadly similar to the existing literature.[67]

The authors emphasize the need to place a higher premium on interventions to promote safe and effective use of lithium among regular users. Methods ranging from use of “lithium cards,” audiovisual aids, smartphone apps, structured education, to concordance therapy may be explored.[1718] Lithium-related interventions should be delivered as part of an integrative psychoeducation program for BD.[18]

However, some important study limitations include a purposive sample from a single center and limited generalizability. The LQ was a tool to elicit descriptive information, rather than a validated scale. The cross-cultural validity of LAQ and MARS is not tested though MARS has been commonly used in Indian studies.

CONCLUSION

The sample was found to be deficient in several critical aspects of knowledge and had moderately negative attitude toward lithium prophylaxis. We emphasize the need for structured interventions to promote safe and effective use of lithium among regular users.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.