l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 2, 26
Asenapine (as Asenapine maleate) 5 mg Sycrest 5mg sublingual
tablets sugar-free | 60 tablet P £102.60 DT = £102.60
Asenapine (as Asenapine maleate) 10 mg Sycrest 10mg sublingual
tablets sugar-free | 60 tablet P £102.60 DT = £102.60
ANTIPSYCHOTICS › LITHIUM SALTS
l CONTRA-INDICATIONS Addison’s disease . cardiac
insufficiency . dehydration . family history of Brugada
syndrome . low sodium diets . personal history of Brugada
syndrome .rhythm disorder. untreated hypothyroidism
treatment (risk of toxicity). elderly (reduce dose). epilepsy
necessary in intercurrent infection (especially if sweating
profusely).review dose as necessary in vomiting . surgery
▶ Long-term use Long-term use of lithium has been
associated with thyroid disorders and mild cognitive and
memory impairment. Long-term treatment should
therefore be undertaken only with careful assessment of
risk and benefit, and with monitoring of thyroid function
every 6 months (more often if there is evidence of
The need for continued therapy should be assessed
regularly and patients should be maintained on lithium
after 3–5 years only if benefit persists.
▶ Rare or very rare Nephropathy
hypertension . leucocytosis . memory loss . movement
SIDE-EFFECTS, FURTHER INFORMATION Overdose Signs of
intoxication require withdrawal of treatment and include
increasing gastro-intestinal disturbances (vomiting,
diarrhoea), visual disturbances, polyuria, muscle
weakness, fine tremor increasing to coarse tremor, CNS
disturbances (confusion and drowsiness increasing to lack
of coordination, restlessness, stupor); abnormal reflexes,
myoclonus, incontinence, hypernatraemia. With severe
356 Mental health disorders BNF 78
blood pressure changes, circulatory failure, renal failure,
coma and sudden death reported.
For details on the management of poisoning, see
Lithium, under Emergency treatment of poisoning p. 1359.
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception during treatment for women of
l PREGNANCY Avoid if possible, particularly in the first
trimester (risk of teratogenicity, including cardiac
Dose adjustments Dose requirements increased during the
second and third trimesters (but on delivery return
Monitoring Close monitoring of serum-lithium
concentration advised in pregnancy (risk of toxicity in
l BREAST FEEDING Present in milk and risk of toxicity in
l RENAL IMPAIRMENT Caution in mild to moderate
impairment. Avoid in severe impairment.
Monitoring In renal impairment monitor serum-lithium
concentration closely and adjust dose accordingly.
▶ Serum concentrations Lithium salts have a narrow
therapeutic/toxic ratio and should therefore not be
prescribed unless facilities for monitoring serum-lithium
Samples should be taken 12 hours after the dose to achieve
a serum-lithium concentration of 0.4–1 mmol/litre (lower
end of the range for maintenance therapy and elderly
A target serum-lithium concentration of 0.8–1 mmol/litre
is recommended for acute episodes of mania, and for
optimum range for each individual patient.
Routine serum-lithium monitoring should be performed
weekly after initiation and after each dose change until
concentrations are stable, then every 3 months thereafter.
Additional serum-lithium measurements should be made
if a patient develops significant intercurrent disease or if
there is a significant change in a patient’s sodium or fluid
▶ Manufacturer advises to assess renal, cardiac, and thyroid
function before treatment initiation.g An ECG is
recommended in patients with cardiovascular disease or
risk factors for it. Body-weight or BMI, serum electrolytes,
and a full blood count should also be measured before
▶ Monitor body-weight or BMI, serum electrolytes, eGFR,
and thyroid function every 6 months during treatment,
and more often if there is evidence of impaired renal or
thyroid function, or raised calcium levels. h
Manufacturer also advises to monitor cardiac function
l TREATMENT CESSATION While there is no clear evidence of
withdrawal or rebound psychosis, abrupt discontinuation
of lithium increases the risk of relapse. If lithium is to be
discontinued, the dose should be reduced gradually over a
period of at least 4 weeks (preferably over a period of up to
3 months). Patients and their carers should be warned of
the risk of relapse if lithium is discontinued abruptly. If
lithium is stopped or is to be discontinued abruptly,
consider changing therapy to an atypical antipsychotic or
l PATIENT AND CARER ADVICE Patients should be advised to
report signs and symptoms of lithium toxicity,
hypothyroidism, renal dysfunction (including polyuria and
polydipsia), and benign intracranial hypertension
(persistent headache and visual disturbance). Maintain
adequate fluid intake and avoid dietary changes which
reduce or increase sodium intake.
Lithium treatment packs A lithium treatment pack should be
given to patients on initiation of treatment with lithium.
The pack consists of a patient information booklet, lithium
alert card, and a record book for tracking serum-lithium
concentration. Packs may be purchased from
Driving and skilled tasks May impair performance of skilled
tasks (e.g. driving, operating machinery).
Treatment and prophylaxis of mania | Treatment and
prophylaxis of bipolar disorder | Treatment and
prophylaxis of recurrent depression | Treatment and
prophylaxis of aggressive or self-harming behaviour
▶ Adult: Dose adjusted according to serum-lithium
concentration, doses are initially divided throughout
the day, but once daily administration is preferred
when serum-lithium concentration stabilised
DOSE EQUIVALENCE AND CONVERSION
▶ Preparations vary widely in bioavailability;
changing the preparation requires the same
precautions as initiation of treatment.
CAMCOLIT ® IMMEDIATE-RELEASE TABLET
Treatment of mania | Treatment of bipolar disorder |
Treatment of recurrent depression | Treatment of
aggressive or self-harming behaviour
▶ Adult: Initially 1–1.5 g daily, dose adjusted according
to serum-lithium concentration, doses are initially
divided throughout the day, but once daily
administration is preferred when serum-lithium
▶ Elderly: Reduce initial dose, dose adjusted according to
serum-lithium concentration, doses are initially
divided throughout the day, but once daily
administration is preferred when serum-lithium
Prophylaxis of mania | Prophylaxis of bipolar disorder |
Prophylaxis of recurrent depression | Prophylaxis of
aggressive or self-harming behaviour
▶ Adult: Initially 300–400 mg daily, dose adjusted
according to serum-lithium concentration, doses are
initially divided throughout the day, but once daily
administration is preferred when serum-lithium
CAMCOLIT ® MODIFIED-RELEASE TABLET
Treatment of mania | Treatment of bipolar disorder |
Treatment of recurrent depression | Treatment of
aggressive or self-harming behaviour
▶ Adult: Initially 1–1.5 g daily, dose adjusted according
to serum-lithium concentration, doses are initially
divided throughout the day, but once daily
administration is preferred when serum-lithium
▶ Elderly: Reduce initial dose, dose adjusted according to
serum-lithium concentration, doses are initially
divided throughout the day, but once daily
administration is preferred when serum-lithium
concentration stabilised continued→
BNF 78 Bipolar disorder and mania 357
Prophylaxis of mania | Prophylaxis of bipolar disorder |
Prophylaxis of recurrent depression | Prophylaxis of
aggressive or self-harming behaviour
▶ Adult: Initially 300–400 mg daily, dose adjusted
according to serum-lithium concentration, doses are
initially divided throughout the day, but once daily
administration is preferred when serum-lithium
Treatment of mania | Treatment of bipolar disorder |
Treatment of recurrent depression | Treatment of
aggressive or self-harming behaviour
▶ Adult: Initially 450–675 mg twice daily, dose adjusted
according to serum-lithium concentration, doses are
initially divided throughout the day, but once daily
administration is preferred when serum-lithium
▶ Elderly: Initially 225 mg twice daily, dose adjusted
according to serum-lithium concentration, doses are
initially divided throughout the day, but once daily
administration is preferred when serum-lithium
Prophylaxis of mania | Prophylaxis of bipolar disorder |
Prophylaxis of recurrent depression | Prophylaxis of
aggressive or self-harming behaviour
▶ Adult: Initially 450 mg twice daily, dose adjusted
according serum-lithium concentration, doses are
initially divided throughout the day, but once daily
administration is preferred when serum-lithium
▶ Elderly: Initially 225 mg twice daily, dose adjusted
according to serum-lithium concentration, doses are
initially divided throughout the day, but once daily
administration is preferred when serum-lithium
Treatment and prophylaxis of mania | Treatment and
prophylaxis of bipolar disorder | Treatment and
prophylaxis of recurrent depression | Treatment and
prophylaxis of aggressive or self-harming behaviour
▶ Adult (body-weight up to 50 kg): Initially 200–400 mg
daily, dose adjusted according to serum-lithium
concentration, doses are initially divided throughout
the day, but once daily administration is preferred
when serum-lithium concentration stabilised
▶ Adult (body-weight 50 kg and above): Initially 0.4–1.2 g
once daily, alternatively initially 0.4–1.2 g daily in
2 divided doses, dose adjusted according to serumlithium concentration, doses are initially divided
throughout the day, but once daily administration is
preferred when serum-lithium concentration stabilised
▶ Elderly: Initially 200–400 mg daily, dose adjusted
according to serum-lithium concentration, doses are
initially divided throughout the day, but once daily
administration is preferred when serum-lithium
l INTERACTIONS → Appendix 1: lithium
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension
CAUTIONARY AND ADVISORY LABELS 10, 25
▶ Camcolit (Essential Pharma Ltd)
Lithium carbonate 400 mg Camcolit 400 modified-release tablets | 100 tablet P £48.18 DT = £4.02
Lithium carbonate 450 mg Liskonum 450mg modified-release
tablets | 60 tablet P £11.84 DT = £11.84
▶ Priadel (lithium carbonate) (Essential Pharma M)
Lithium carbonate 200 mg Priadel 200mg modified-release tablets
| 100 tablet P £2.76 DT = £2.76
Lithium carbonate 400 mg Priadel 400mg modified-release tablets
| 100 tablet P £4.02 DT = £4.02
CAUTIONARY AND ADVISORY LABELS 10
▶ Lithium carbonate (Non-proprietary)
Lithium carbonate 250 mg Lithium carbonate 250mg tablets | 100 tablet P £87.00 DT = £87.00
Treatment and prophylaxis of mania | Treatment and
prophylaxis of bipolar disorder | Treatment and
prophylaxis of recurrent depression | Treatment and
prophylaxis of aggressive or self-harming behaviour
▶ Adult: Dose adjusted according to serum-lithium
concentration; doses are initially divided throughout
the day, but once daily administration is preferred
when serum-lithium concentration stabilised
DOSE EQUIVALENCE AND CONVERSION
▶ Preparations vary widely in bioavailability;
changing the preparation requires the same
precautions as initiation of treatment.
Treatment and prophylaxis of mania | Treatment and
prophylaxis of bipolar disorder | Treatment and
prophylaxis of recurrent depression | Treatment and
prophylaxis of aggressive or self-harming behaviour
▶ Adult (body-weight up to 50 kg): Initially 509 mg daily in
2 divided doses, dose adjusted according to serumlithium concentration
▶ Adult (body-weight 50 kg and above): Initially
1.018–3.054 g daily in 2 divided doses, dose adjusted
according to serum-lithium concentration
▶ Elderly: Initially 509 mg daily in 2 divided doses, dose
adjusted according to serum-lithium concentration
DOSE EQUIVALENCE AND CONVERSION
▶ For Li-Liquid ®: Lithium citrate tetrahydrate 509 mg is
equivalent to lithium carbonate 200 mg.
Treatment and prophylaxis of mania | Treatment and
prophylaxis of bipolar disorder | Treatment and
prophylaxis of recurrent depression | Treatment and
prophylaxis of aggressive or self-harming behaviour
▶ Adult (body-weight up to 50 kg): Initially 520 mg twice
daily, dose adjusted according to serum-lithium
concentration, doses are initially divided throughout
the day, but once daily administration is preferred
when serum-lithium concentration stabilised
▶ Adult (body-weight 50 kg and above): Initially
1.04–3.12 g daily in 2 divided doses, dose adjusted
according to serum-lithium concentration, doses are
initially divided throughout the day, but once daily
administration is preferred when serum-lithium
▶ Elderly: Initially 520 mg twice daily, dose adjusted
according to serum-lithium concentration, doses are
initially divided throughout the day, but once daily
administration is preferred when serum-lithium
358 Mental health disorders BNF 78
DOSE EQUIVALENCE AND CONVERSION
▶ For Priadel ® liquid : Lithium citrate tetrahydrate
520 mg is equivalent to lithium carbonate 204 mg.
l INTERACTIONS → Appendix 1: lithium
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 10
▶ Li-Liquid (Rosemont Pharmaceuticals Ltd)
Lithium citrate 101.8 mg per 1 ml Li-Liquid 509mg/5ml oral
solution | 150 ml P £5.79 DT = £5.79
Lithium citrate 203.6 mg per 1 ml Li-Liquid 1.018g/5ml oral
solution | 150 ml P £11.58 DT = £11.58
▶ Priadel (lithium citrate) (Essential Pharma M)
Lithium citrate 104 mg per 1 ml Priadel 520mg/5ml liquid sugarfree | 150 ml P £6.73 DT = £6.73
Antidepressant drugs are effective for treating moderate to
severe depression associated with psychomotor and
physiological changes such as loss of appetite and sleep
disturbance; improvement in sleep is usually the first benefit
of therapy. Ideally, patients with moderate to severe
depression should be treated with psychological therapy in
addition to drug therapy. Antidepressant drugs are also
effective for dysthymia (lower grade chronic depression
(typically of at least 2 years duration)).
Antidepressant drugs should not be used routinely in mild
depression, and psychological therapy should be considered
initially; however, a trial of antidepressant therapy may be
considered in cases refractory to psychological treatments or
in those associated with psychosocial or medical problems.
Drug treatment of mild depression may also be considered in
patients with a history of moderate or severe depression.
The major classes of antidepressant drugs include the
tricyclic and related antidepressants, the selective serotonin
re-uptake inhibitors (SSRIs), and the monoamine oxidase
inhibitors (MAOIs). A number of antidepressant drugs
cannot be accommodated easily into this classification.
There is little to choose between the different classes of
antidepressant drugs in terms of efficacy, so choice should be
based on the individual patient’s requirements, including
the presence of concomitant disease, existing therapy,
suicide risk, and previous response to antidepressant
therapy. Since there may be an interval of 2 weeks before the
antidepressant action takes place, electroconvulsive
treatment may be required in severe depression when delay
is hazardous or intolerable. During the first few weeks of
treatment, there is an increased potential for agitation,
anxiety, and suicidal ideation.
SSRIs are better tolerated and are safer in overdose than
other classes of antidepressants and should be considered
first-line for treating depression. In patients with unstable
angina or who have had a recent myocardial infarction,
sertraline p. 367 has been shown to be safe.
Tricyclic antidepressants have similar efficacy to SSRIs but
are more likely to be discontinued because of side-effects;
toxicity in overdosage is also a problem. SSRIs are less
sedating and have fewer antimuscarinic and cardiotoxic
effects than tricyclic antidepressants.
MAOIs have dangerous interactions with some foods and
drugs, and should be reserved for use by specialists.
Although anxiety is often present in depressive illness (and
may be the presenting symptom), the use of an antipsychotic
or an anxiolytic may mask the true diagnosis. Anxiolytics or
antipsychotic drugs should therefore be used with caution in
depression but they are useful adjuncts in agitated patients.
Augmenting antidepressants with antipsychotics under
specialist supervision may also be necessary in patients who
have depression with psychotic symptoms.
St John’s wort (Hypericum perforatum) is a popular herbal
remedy on sale to the public for treating mild depression. It
should not be prescribed or recommended for depression
because St John’s wort can induce drug metabolising
enzymes and a number of important interactions with
conventional drugs, including conventional antidepressants,
have been identified. Furthermore, the amount of active
ingredient varies between different preparations of St John’s
wort and switching from one to another can change the
degree of enzyme induction. If a patient stops taking St
John’s wort, the concentration of interacting drugs may
increase, leading to toxicity.
Patients should be reviewed every 1–2 weeks at the start of
antidepressant treatment. Treatment should be continued
for at least 4 weeks (6 weeks in the elderly) before
considering whether to switch antidepressant due to lack of
efficacy. In cases of partial response, continue for a further
2–4 weeks (elderly patients may take longer to respond).
Following remission, antidepressant treatment should be
continued at the same dose for at least 6 months (about
12 months in the elderly), or for at least 12 months in
patients receiving treatment for generalised anxiety disorder
(as the likelihood of relapse is high). Patients with a history
of recurrent depression should receive maintenance
treatment for at least 2 years.
Hyponatraemia and antidepressant therapy
Hyponatraemia (usually in the elderly and possibly due to
inappropriate secretion of antidiuretic hormone) has been
associated with all types of antidepressants; however, it has
been reported more frequently with SSRIs than with other
antidepressants. Hyponatraemia should be considered in all
patients who develop drowsiness, confusion, or convulsions
while taking an antidepressant.
Suicidal behaviour and antidepressant therapy
The use of antidepressants has been linked with suicidal
thoughts and behaviour; children, young adults, and
patients with a history of suicidal behaviour are particularly
at risk. Where necessary patients should be monitored for
suicidal behaviour, self-harm, or hostility, particularly at the
beginning of treatment or if the dose is changed.
Serotonin syndrome or serotonin toxicity is a relatively
uncommon adverse drug reaction caused by excessive
central and peripheral serotonergic activity. Onset of
symptoms, which range from mild to lifethreatening, can
occur within hours or days following the initiation, dose
escalation, or overdose of a serotonergic drug, the addition
of a new serotonergic drug, or the replacement of one
serotonergic drug by another without allowing a long
enough washout period in-between, particularly when the
occurs with a combination of serotonergic drugs, one of
The characteristic symptoms of serotonin syndrome fall
into 3 main areas, although features from each group may
not be seen in all patients—neuromuscular hyperactivity
(such as tremor, hyperreflexia, clonus, myoclonus, rigidity),
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