Bipolar disorder and lithium

Case summary

Background (age, sex, occupation, baseline function)

67-year-old retired female

History of presentation/reason for review

Attends the practice for a routine medication review

Current medical history and relevant co-morbidities

Nocturnal leg cramps – 18 months ago
Hypertension – 20 years ago
Primary hypercholesterolaemia – 20 years ago
Bipolar Type 1 disorder – 38 years ago

Current medication and drug allergies (include over the counter (OTC) preparation, traditional medicines and herbal remedies)

Allergies or adverse drugs reactions (ADRs): nil

Currently prescribed:

Atorvastatin 20mg tablets: one tablet daily
Lithium (Priadel®) 400mg tablets: two tablets at night
Quinine sulfate 200mg tablets: one tablet at night
Ramipril 10mg capsules: one capsule daily (increased two months prior to review)

Over the counter medicines: none except ibuprofen, “simple painkillers”, but none taken in recent months. Does not take any herbal remedies or street drugs

Lifestyle and current function

Keeps active (walking)
Clinical Frailty Score (Rockwood) 3 (managing well)
Drinks around five units of alcohol per week, although reports this can vary considerably
Does not smoke

“What matters to me” (ideas, concerns and expectations of treatment)

She is happy with current therapy and feels medicines are working well and reports no concerns.

Observations, examinations and results

Note: local laboratory reference ranges may vary

Examination

Drowsiness and fine tremor noted – no other concerns noted at mental state examination (no other obvious concerns in appearance, behaviour, speech, thought form/content, perception, cognition, insight, mood and capacity)

Recent blood tests

Weight 64kg, Height 163cm, BMI 24kg/m²
Average home blood pressure reading: 164/88mmgHg (8 weeks prior to review); 134/84mmHg (4 weeks prior to review)
Urea and Electrolytes satisfactory with no deterioration in eGFR
Creatinine 70micromol/L (60-120micromol/L), eGFR greater than 60ml/min/1.73m²
Cholesterol within normal range (on current treatment)
LFTs, TSH, bone profile within normal ranges
Lithium levels (0.4–1mmol/L):
- 98mmol/L (two weeks prior to review)
- 90mmol/L (four months prior to review)
- 82mmol/L (one year prior to review)
- 70mmol/L (four years prior to review)
- 72mmol/L (six years prior to review)

Most recent relevant consultations

Ramipril increased eight weeks prior to review due to uncontrolled hypertension
Recent psychiatry letter noting that her mental state has been stable for over seven years

7 steps: Person specific issues to address

1. Aims: What matters to the individual about their condition(s)?

Review diagnoses and consider:

Therapeutic objectives of drug therapy
Management of existing health problems
Prevention of future health issues, including lifestyle advice

Ask person to complete PROMs (Questions to answer before medicines review) before their review

Person specific issues to address

Continued stability of Bipolar type 1 disorder
Reduction of risk of cardiovascular events

2. Need: Identify essential drug therapy

Identify essential drugs (not to be stopped without specialist advice)

Drugs that have essential replacement functions (e.g. levothyroxine)
Drugs to prevent rapid symptomatic decline (e.g. drugs for Parkinson’s disease, heart failure)

Person specific issues to address

Lithium - Stopping lithium therapy could cause a relapse in bipolar symptoms and significantly increase suicide risk – do not stop without specialist advice

3. Does the individual take unnecessary drug therapy?

Identify and review the continued need for drugs

what is medication for?
with temporary indications
with higher than usual maintenance doses
with limited benefit/evidence for use
with limited benefit in the person under review (see Drug efficacy & applicability (NNT) table)

Person specific issues to address

Quinine - assess ongoing benefit. Individual at risk of side effects including QTc prolongation

4. Effectiveness: Are therapeutic objectives being achieved?

Identify the need for adding/intensifying drug therapy to achieve therapeutic objectives

to achieve symptom control
to achieve biochemical/clinical targets
to prevent disease progression/exacerbation
is there a more appropriate medication to achieve goals?

Person specific issues to address

No changes required

5. Safety: Does the individual have or is at risk of ADR/ side effects? Does the patient know what to do if they’re ill?

Identify individual safety risks by checking for

appropriate individual targets e.g. HbA1c, BP
drug-disease interactions
drug-drug interactions (see ADR table)
monitoring mechanisms for high-risk drugs
risk of accidental overdosing

Identify adverse drug effects by checking for

specific symptoms/laboratory markers (e.g. hypokalaemia)
cumulative adverse drug effects (see ADR table)
drugs used to treat side effects caused by other drugs

Medication Sick Day guidance

Ensure discussion and clear information on which medicines to withhold at times of dehydrating illness

Person specific issues to address

Lithium – despite the level being in therapeutic range, it is rising and appears to be higher than required to manage bipolar type 1 disorder (see key concepts below)
Interaction with ibuprofen: occasionally buys OTC
Interaction with ramipril could influence lithium level. Option to change to other medication e.g. amlodipine
Alcohol consumption and lithium combined can impair psychomotor skills – this varies significantly between individuals
Dehydration can influence development of lithium toxicity. This can be exacerbated by alcohol
Lithium and quinine could both prolong QTc interval. Risk increases in females and increases with age. Consider ECG to assess QTc
Medication Sick Day Guidance: ensure clear information provided on medicines to withhold if dehydrated (in this case ramipril)

6. Sustainability: Is drug therapy cost-effective and environmentally sustainable?

Identify unnecessarily costly drug therapy by

considering more cost-effective alternatives, formulary choices, safety, convenience

Consider the environmental impact of

Inhaler use
Single use plastics
Medicines waste
- over-ordering
- disposal
Water pollution

Person specific issues to address

All medicines are formulary choices
Advised to dispose of medicines through the community pharmacy
Advised to only order what is needed, do not stockpile medicines

7. Person-centredness: Is the person willing and able to take drug therapy as intended?

Does the person understand the outcomes of the review?

Consider Teach back

Ensure drug therapy changes are tailored to individual’s preferences. Consider

is the medication in a form they can take?
is the dosing schedule convenient?
what assistance is needed?
are they able to take medicines as intended?

Agree and communicate plan

discuss and agree with the individual/carer/welfare proxy therapeutic objectives and treatment priorities
include lifestyle and holistic management goals
inform relevant health and social care providers of changes in treatments across the transitions of care

Ask person to complete PROMs (Questions to answer after medicines review) after their review

Agreed plan

Stop: ibuprofen and quinine sulfate
Change: ramipril to amlodipine
Individual re-counselled on lithium including signs and symptoms of toxicity and how medication/diet can influence this.
Lithium levels (and blood pressure) to be repeated in two weeks and if still elevated, lithium to be reduced by 100-200mg. Individual’s mental state to be monitored at each review – also advised to report any deterioration in mental state
Education on importance of presenting National Patient Safety Agency (NPSA) purple lithium warning card to community pharmacy when purchasing any OTC medicines (see key concepts)
Advise on the avoidance of dehydration e.g. when drinking alcohol and the importance of drinking other fluids

Key concepts in this case

It is important to look at trends in lithium levels rather than individual levels, and how this relates to the person’s mental health. In this case the bipolar disorder was managed adequately at lithium levels around 0.7mmol/L and despite the recent level (0.98mmol/L) being in reference range, the dose may be kept at an unnecessarily high level. This puts them at increased risk of side effects (e.g. fine tremor, drowsiness). Given the length of time her mood has been stabilised, levels lower than 0.7mmol/L could also be considered
It generally takes five to seven days for lithium levels to fully adjust. Therefore, levels should be taken after at least five days on any new dosage regimen. In some scenarios (such as a recent overdose) a level earlier than five days may be obtained to establish whether lithium levels are trending upwards or downwards. As there was no urgency in this scenario, two weeks was chosen. Levels should ideally be taken 12 hours post dose (if on twice daily regimen the dose should be delayed allowing for this)
Lithium follows linear pharmacokinetics and dose reductions should be made accordingly. Specialist mental health teams should be contacted for advice where required. If any dose reduction is made to lithium, the individual’s mental state should be monitored during this transition period for any deterioration.
Individuals should be counselled on lithium including importance of monitoring, signs and symptoms of toxicity and factors that can influence lithium levels.
Medication interactions and dehydration are common factors that increase lithium levels.
Individuals should be offered the National Patient Safety Agency (NPSA) patient information (or similar). This includes a lithium record booklet and alert card. This card can be a useful prompt to individuals and healthcare professionals supplying or prescribing medications to take into account potential interactions. In this case it might have avoided ibuprofen being purchased in addition to lithium
Individuals may require medication combinations which interact with lithium (resulting in higher lithium levels). If so, it is important they are fully aware of the risk and fully understand the signs and symptoms of toxicity, and what to do should these occur. More frequent monitoring could be considered.
Several medications can prolong the QTc interval. It is important to identify these (especially in at risk individuals) and discuss any additional risk with therapy, or alternative treatment options where available.
Other points to consider as part of a comprehensive polypharmacy review are:

Appropriateness of quinine in leg cramps

Hypertension management including the impact of NSAIDs