ACUTE MANIA AND

BIPOLAR
Bipolar Disorders
Relapsing/remitting condition characterised by periods
of elated mood (mania/hypomania) and depressed
mood
Mania
Mood that is predominantly elevated, expansive or irritable & definitely
abnormal for the individual
At least 3 of the following should be present (4 or more if mood is irritable)
Increased activity or physical restlessness
Increased talkativeness
Flight of ideas or the subjective experience of thoughts racing
Loss of normal social inhibitions resulting in behaviour that is inappropriate for the
circumstances
Decreased need for sleep
Inflated idea of self importance or grandiosity
Distractibility or constant change in plans
Behaviour that is ill-advised or reckless, and whose risks the subject does not recognise
Marked sexual energy &/or promiscuity
Organic mood disorder
Usually depression Usually mania Either depression or
mania
Cushings disease Hyperthyroidism Multiple sclerosis
Addisons disease Steroids CVD
Hypothyroidism Amphetamines (acute) SLE
Hypercalcaemia L-Dopa Epilepsy
Diabetes mellitus Bromocriptine Brain tumours
Carcinomas Isoniazid
congestive cardiac failure
Post infective states
Beta blockers
Benzodiazepines
Digoxin
General approach to treatment
Pharmacotherapy

Medications used to manage patients with bipolar disorder include the following:
Benzodiazepines - for acute agitation (e.g. lorazepam, clonazepam)
Antimanic agents (e.g. lithium)
Anticonvulsants (e.g. carbamazepine, valproate sodium, valproic acid, divalproex sodium, lamotrigine)
First-generation antipsychotics (, haloperidol)
Second-generation antipsychotics (e.g. asenapine, ziprasidone, quetiapine, risperidone, aripiprazole, olanzapine,
olanzapine and fluoxetine, clozapine, paliperidone)
Phenothiazineantipsychotics (e.g. chlorpromazine)
Dopamine agonists (e.g. pramipexole)

Nonpharmacotherapy

Psychotherapy may help to decrease relapse rates, improve quality of life, and/or increase functioning, or more
favorable symptom improvement.
Electroconvulsive therapy may be useful in selected patients with bipolar disorder.
Case 1: Sophie
Sophie, aged 24 years, lives alone and works as an article clerk in a large
corporate law firm. You have been her GP since she was a young child, but
have seen her infrequently over the years. She has no known psychiatric
history.
Sophie says she has been struggling with low mood recently. She feels heavy
and tired, and she has been frequently tearful. She has been sleeping
excessively, resulting in frequent lateness to work, and comfort eating, with 4
5 kgs of weight gain. She feels unable to cope with work, lamenting that she
has wasted the opportunities her parents worked so hard to give her.
Sophie was socially active throughout her university years, but has become
increasingly withdrawn and stayed at home over the previous 2 months. She
has started drinking at least a bottle of wine each night just to forget about
how Ive stuffed everything up and about how pathetic I am.
 What further information do you need in order to make
a diagnosis?
Sophie reports that she was pretty down during her final
year of high school and a couple of times in university,
but says that she had not suffered from any significant
depression in the past.
She is physically well.
Her childhood was relatively uneventful.
The only family psychiatric history is a maternal aunt who
had manic depression.
 What is your working diagnosis?
Differential Diagnosis
MDD
Persistent Depressive disorder (dysthymia)
Major depression due to a general medical condition
Substance induced depression or substance misuse
comorbid with depression
Bipolar disorder
Prodromal symptoms of a psychosis
Alcohol abuse or dependence
Diagnosis and management
You diagnose an MDE and assess risk. Your management includes commencing venlafaxine
75 mg daily. You arrange to review Sophie again in 2 weeks.
However, in the meantime, you are called by a psychiatry registrar at the hospital nearby,
where Sophie has been admitted with a manic episode. She had not been sleeping and was
giving friends expensive gifts, dressing in flamboyant and provocative clothes at work and
acting strangely. Her parents called the crisis team when she contacted them late one night
to excitedly say goodbye as she believed she had been asked to report to duty by the secret
service to save the world.
They reported that Sophie experienced a similar episode when she was in her first year at
university. However, Sophies behaviour at that time had not been quite as erratic and had
settled after 4 or 5 days. In hospital, venlafaxine was ceased. Lithium and olanzapine were
commenced, effectively treating the manic and psychotic symptoms.
You receive a discharge summary cautioning against further use of antidepressant medication
and requesting you check Sophies serum lithium levels, but little other followup advice.
Sophie sees you 2 weeks after discharge and appears to be doing well.
 What is your revised diagnosis?
You arrange to see Sophie monthly. One month later she
has returned to work, but still experiences a low mood at
times. She is worried about what a diagnosis of bipolar
disorder means for her future and often thinks about her
behaviour when she was an inpatient, feeling very
embarrassed.
She is also having trouble sleeping. She ceased
olanzapine as she believed it hampered her ability to
think properly at work.
You are concerned that Sophie has some residual
depressive symptoms and has not returned to the mental
 How would you manage Sophie?
 Case 2
Presentation
Mr Jakob C is a 31-year-old lawyer who presents with a
one-week history of elevated mood, racing thoughts,
reduced need for sleep and grandiose plans. Jakob is
accompanied by his fiance, who is concerned that he
will soon be dismissed from his top-tier law firm unless
he obtains some effective treatment. She also reports
that Jakob has been over-spending and has been much
more interested in sex than is usual for him. She thinks
he is now working on a "crazy scheme" to make them
both very wealthy.

What hypotheses are you considering at this
point?
What mechanisms could lead to these symptoms
and signs?
What further history would you like to obtain and
what examinations would you like to perform?
History
Jakob reported that he had not experienced anything like this before, apart
from when he had had a few hours of elevated mood when he experimented
with amphetamines at a party a few years before. However, his fiance
reported that over the past few years she had observed several episodes of
low mood that seemed to last for months at a time. Although these were not
severe and had not required medical treatment, she said that Jakob had self-
medicated with caffeine and alcohol.

Jakob denied any past medical history and reported that he was on no
prescribed medication. He denied recent use of illicit substances, although
had used cannabis on a semi-regular basis while at university. He reported
drinking 7-10 standard measures of alcohol per week. He was a non-smoker.
He drank six cups of coffee daily.

His fiance reported that Jakob's uncle had killed himself in his mid-thirties,
although she was not sure whether he had ever been diagnosed with a
mental disorder.
Examination
On mental state examination, Jakob appeared restless and distractible. He
was over-talkative and he flitted from one topic to another. He expressed
irritation at the duration of the interview and said that he had better things
to do with his time. He appeared preoccupied with a scheme to build a
tunnel under the Bay to Moreton Island so that the land there could be
developed. There were no obvious perceptual abnormalities evident. There
was no clouding of consciousness. His insight and judgement were quite
impaired.

Physical examination was unremarkable.

A urine sample was taken to screen for drugs of abuse. A blood sample was
taken for serum biochemistry. However, these results were not yet available.
 Does Jakob have Bipolar or something else?
Does he need hospitalisation, or could he be managed
as an outpatient?
If Jakob is hospitalized, should he be managed as a
voluntary or involuntary patient? Discuss the pros and
cons of your decision.
On the basis of the information provided in this
vignette, what specific risks are already evident?
What therapeutic interventions are indicated?
.
Management

Jakob C was admitted to hospital as an involuntary

patient under the Mental Health Act. He was placed on
15-minute visual observations, without leave privileges.
His provisional diagnosis was Bipolar 1 Disorder.

His initial management included administration of

risperidone and the benzodiazepine sedative
lorazepam. His disturbed mental state precluded any
significant psychoeducation and formal psychotherapy
was not indicated acutely.
Management cont.

When his screening biochemistry results were available, showing

normal renal and thyroid function, he was commenced on the
mood stabiliser lithium carbonate. Despite this treatment, his
mental state deteriorated over the next few days and he
developed further mood elevation, together with marked agitation
and assaultative behaviour. He was placed in a high dependency
area to reduce external stimulation and to minimise the risk to
himself and others.
He also required intermittent seclusion.

His urine drug screening results came back, showing low levels of
tetrahydrocannabinoids (THC).
are the common adverse effects of risperidone?What precautions need to be taken when prescribing loraze
are the common adverse effects of lithium carbonate at therapeutic serum levels?.
are the common manifestations of lithium toxicity?.
mood stabilisers can be used instead of lithium carbonate?
re any place for the use of electroconvulsive therapy (ECT) in the management of acute mania?
the discovery of THC in his urine drug screen, do you think that Jakob should be referred to the
ol and drugs service?
THC likely to be implicated in his manic presentation?
ANTIPSYCHOTIC DRUGS
The Dopamine Hypothesis: pyschosis (eps schiz) caused by functional excess of dopamine in se
neuronal tracts in the brain.
Dopamine receptors: 5 types D1-D5 The D2 receptor is negatively coupled to adenylate cyclase.
Older antipsychotics have mainly D2 receptor affinity.
Other receptors: most of the newer antipsychoics have higher affinities for receptors other
than D2.eg alpha adrenoreceptor blocking of many drugs,
Clozapine had D4 abd 5HT2 receptor blocking action.
Most atypical drugs have high affinity for 5HT2 a receptors, but have some D2 activity.

So DOPAMINE receptor BLOCKADE is the major effect that correlates with benefits from classic anti
Dopamine tracts include:
Mesocortical-mesolimbic (mood and mentation)
Nigrostriatla (extrapyramidal)
Chemoreceptor trigger zone emesis.
Tuberinfundibular prolactin
ANITPSYCHOTIC DRUGS

Classic (D2 receptor)

Phenothiazines (chlorpromazine, thioridizine, fluphenazine)
Thioxanthines (thiothixine)
Butyorphenones (haloperidaol)
Newer agents (heterocyclic) atypical antipsychotics 5HT2
receptor affinity
Clozapine, olanzapine, respiridone, quetiapine, loxapine
All are lipid soluble and enter CNS easily.
They are liver metabolized, an have long plasma half lives.
 Adverse effects

extrapyramidal SE, Parkinson like syndrome, -esp haloperidol, fluphenizine.

Tardive dyskinesias choreoathetoid lip movements (can develop after years ), dystonic reactions.
Autonomic effects: muscarinic (dry mouth constipation urinary retention etc) alpha blockade :postural hypotension
Endocrine and metabolic : gynacomastia, amenhorrea-galactorrhea, weight gain, hyperglycemia
Neuroleptic malignant syndrome malignant hyperthermia , ALOC, tachycardia, rigidity, sweating, fever, (old and n
Sedation esp phenothiazines
Miscellaneous toxicity: thioridizine retinal deposits visual impairment.\;atypicals cause QT prologation on ECG,
Clozapine may cause agranulocytosis
the new generation drugs cause less extrapyramicdal side effects but can cause tardive dyskinesia.
Overdose toxicity : thioridazine can be fatal, others have seizures, hyptersion long QT interval , dose dependant se
LITHIUM

Rapidly absorbed and distributed to body water; cleared by kidneys Half life 20
hours.Target concentration .8 -1.2 mEq/LDEhydration or treatment with other
meds (thiazides, NSAIDS, ACE inhibitors, Loop diuretics can result in toxic levels.
Low therapeutic Index :ie toxic/theraptutic ratio
Levels are checked regularly
Side effects: metallic taste, fatigue, polydipsia, N and V, D, muscle weakness
oedema.

Mechanism of action not well defined. Postulated that it inhibits inositol
monophosphatase, rate limiting enz in reactions to reduce synaptic transmission.
Onset of alteration of mainia is slow so often require antipschotics/benzos at the
start.Na Valpoate and olanzapine equally effective in acute mania as lithium.
Toxicity hyperreflexia,pshycoisis, fits syncope, oliguria

Investigations

Full blood count (FBC or FBE) to check for anaemia

Multiple biochemical screen (E/LFTs or similar) to check for electrolyte abnormalities
& evidence of organ failure
Thyroid stimulating hormone (TSH) to exclude hypothyroidism
Serum vitamin B12 to exclude vitamin B12 deficiency
Serum folate to exclude folate deficiency
Electrocardiogram (ECG) to check QTc interval (some antidepressants prolong QTc
interval)
Brain scan (CT or MRI) to assess extent of cerebrovascular disease & rule out space
occupying lesions
In patients with recurrent episodes of depression, fewer investigations would be
undertaken.
A more extensive list of investigations might be undertaken in situations where there
are appropriate clinical indications.