- SSRI (selective serotonin reuptake
inhibitor; fluoxetine, sertraline)
- SNRI (serotonin (and) noradrenaline
reuptake inhibitor; venlafaxine)
- Tricyclic (amitriptyline)
- Monoamine oxidase inhibitor (phenelzine)
- risperidone
- olanzapine
- quetiapine
- haloperidol
- flupentixol
- chlorpromazine
Hypnotic (and reversal) agents
- Benzodiazepine (temazepam; diazepam,
midazolam (iv); restless legs:
- clonazepam)
- Cyclopyrrolone (zoplicone)
- Reversal (benzodiazepine) agent
Mood stabilizer
- Carbamazepine
- Lithium (LEVELS)
Ali Black
Ali Black
Ali Black
Ali Black
Alan McLeod
Alan McLeod
Alan McLeod
Alan McLeod
Alan McLeod
Alan McLeod
Alan McLeod
Alan McLeod
Alan McLeod
Alan McLeod
Ali Black
Ali Black
 ?Increased risk of suicide in first 2 weeks, due to improved motivation but lag in
improvement of mood.
 Increase dose gradually over 2-3 weeks
 Withdraw dose gradually over 2-3 weeks
 Recommended 6m treatment for 1st episode, longer for recurrence
 Regular follow-up: 2 weeks, then another 1 month, 2 monthly
 Symptoms improve 2-6 weeks, change drug after 4 weeks if no improvement
 Prescribe in small quantities (e.g. 1 week) especially TCAs
NICE Guidelines
Classify depression according to number of ICD10 symptoms:
Not depressed = <4
Mild = 4
Moderate = 5-6
Severe = 7 or more
Severe with psychotic symptoms
Symptoms should be present for a month or more, for most of the day.
Consider whether it is:
1st presentation
Recurrent depression
Treatment resistant depression.
See NICE guidelines:
E.g Fluoxetine (Prozac) Sertraline
Selective seratonin re-uptake inhibitors.
Fluoxetine Indications: Can be used in under 18’s (the only SSRI that can)
 1st line for depressive illness, 20mg to start, increase at 3 week intervals by 20mg to max
 OCD, 20mg to start, increase at 2 week intervals to max 60mg OD
 Bulimia nervosa, 60mg OD, can increase to 80mg
Sertraline Indications: depressive illness, PTSD in women, OCD
Contra-indications of all SSRIs:
 Manic phase,
 MAOIs within 2 weeks (dangerous ‘seratonin reaction’: CVS collapse, muscle rigidity,
 Simultaneous TCA use (inhibits TCA hepatic metabolism)
Side effects of SSRIs: less sedative, fewer antimuscarinic and cardiotoxic than TCAs
 GI: nausea and vomiting, dyspepsia, diarrhoea, constipation, appetite change
 Skin: rash, photosensitivity
 Insomnia
 Headache
 Dry mouth
 Loss libido, anorgasmia
Venlafaxine by Ali Black
SNRI (seratonin and noradrenaline reuptake inhibitor)
Potent inhibitors of neuronal serotonin and noradrenaline reuptake and weak inhibitors of
dopamine reuptake.
Venlafaxine has less affinity for muscarinic, histaminergic, and alpha1-adrenergic receptors in
vitro than other psychiatric drugs. This may explain lesser side effect profile seen with
Venlafaxine, compared to the various anticholinergic, sedative, and cardiovascular effects
seen with other psychotropic drugs.
Severe depressive illness/treatment resistant
Generalised anxiety disorder
Depression, initially 75mg in 2 divided doses, then 150mg after 2-3 weeks in divided dose. If
in hospital & very severe, may start 150mg, up to 375mg, then gradually reduce. Not for
under 18 yrs age.
GAD, 75mg divided, daily.
Breast feeding
Hepatic impairment
Renal impairment
Cardiac disease
Careful monitoring of BP as may cause hypertension
ECG prior to commencement
Common s/e:
 nausea and vomiting
 diarrhoea,
 headache,
 insomnia,
 agitation,
 abnormal ejaculation/orgasm and impotence in men
 cardiotoxicity
MAOI (within 2 weeks), CBZ, Phenytoin, benzos, Li, ?Warfarin
NICE Guidelines:
 Baseline ECG and BP, plus regular BP monitoring
 Use only by secondary care specialists, or GP with mental health special interest.
 Not used as 1st line in depression, more for treatment resistant
Amitriptyline by Ali Black
Tricyclic antidepressant
TCAs competitively block neuronal re-uptake of noradrenaline and/or seratonin into the presynaptic neurone, increasing the longevity of transmitter in the synapse. Eventually there is
down-regulation of receptors in the brain.
Amitriptyline indications and dosage:
Depression, initially 75mg as divided dose, or in one dose nocte.
Increase gradually to 150-200mg. Do not use for depression in under 16yrs age.
Especially useful where there is insomnia, due to sedative effects.
Bedwetting in children, 7-10yrs 10-20mg nocte, 11-16yrs 25-50mg nocte, max 3 months.
Gradual withdrawal.
Neuropathic pain (.g. phantom limb, postherpetic neuralgia, peripheral neuopathy, TMJ joint
pain etc) initially 10-25mg nocte, max 75mg.
Recent MI
Arrhythmias (especially heart block)
Severe liver disease
Side effects (many):
Drowsiness (give at night, avoid driving, machinery etc)
Anticholinergic: dry mouth, constipation, blurred vision
Poor concentration (drowsiness)
Postural hypotension and syncope
ECG changes and arhhythmia
Confusion (esp. elderly)
Movement disorder
Testicular enlargement, gynaecomastia, galactorrhoea
Abnormal LFT & jaundice
Interference sexual function
Increased appetite and weight gain
Therepeutic effect takes 3 weeks approx. Suicide by OD is a high risk as motivation improves,
but mood may still be low- careful monitoring advised, and prescribe few tablets at a time.
Drowsiness may be dangerous depending on job, e.g long distance driving.
Tricyclic Overdose Management
Symptoms and signs:
Hyper-reflexia & upgoing plantars
Respiratory failure
Pupil dilation
Metabolic acidosis
Delirium and confusion
Urinary retention
ITU if severe
Supportive: ventilation to correct hypoxia
Activated charcoal
IV diazepam if convulsing, oral if agitation only
Antiarrhythmics not used: treating acidosis and hypoxia should correct.
Phenelzine by Ali Black
Monoamine Oxidase Inhibitor
Monoamine oxidase acts in the synapses, and breaks down noradrenaline and seratonin.
Thus MAO inhibitors increase noradrenaline and seratonin levels.
MAOIS are irreversible, non-competitive antagonists of monoamine oxidase (MAO) type A, in
the brain, peripheral neurones, enterocytes of the gut, and platelets.
Rarely used now due to s/e, and newer better drugs, but indicated in:
 Failure of other antidepressants
 Phobic states
 Agitated depression
Side effects:
due to widespread enzyme inhibition:
 Postural hypotension
 Headache
 Anticholinergic s/e
 Drug-induced hepatitis (esp. phenelzine)
 Hypertensive crisis
Diet restriction
 Affects continue 2-3 weeks after stopping drug: this is because it takes this long to
synthesise new MAO.
Hypertensive crisis: Following ingestion of amine-containing foods and drinks and drugs,
MAO normally metabolises tyramine to harmless products during absorption. When MAOIs
are used, Tyramine is taken up by peripheral sympathetic nerve endings, where it displaces
stored endogenous noradrenaline (sympathomimetic effect: stimulates the sympathetic
system)  hypertension, tachycardia and headache. If severe, may cause CVA.
AVOID cheese, meat, yeast, red wine.
There are new reversible MAOIs which may be of more use as they are safer (moclobomide).
4-16 mg daily
As low as 1 or 2
may be useful
5-20 mg daily
25 mg bds day 1
50 mg bds day 2
100 mg bds day 3
150 mg bds day 4
Max 750 mg daily
3-9 mg bd
Max 18 mg daily
20-40 mg every
2-4 weeks depot*
1-3 mg bds/tds
5-5 mg bds/tds in
symptoms up to
max of 30
50-300 mg every
4 weeks as depot*
Side effects
Possible diabetes
Increased risk of stroke in
the elderly
Insomnia, agitation,
Increased risk of stroke in
the elderly
Speech difficulties
May soon be
recategorised as a
typical. ‘typical’ side
effect profile seen with
increasing doses esp
over 6 mg.
Not licensed for acute
Less sedating.
More extrapyramidal.
Esp with withdrawal &
apathy; not mania.
Less sedative.
Extrapyramidal sympt.
more common.
Most effective drug for
positive symptoms.
Also for motor tics and
Less sedating.
Fewer antimuscarinic or
hypotensive symptoms.
Also for mania –
different dose
More extrapyramidal.
*Depot agents are administered by deep intramuscular injection. They may be used in
patients who are poorly compliant but may give rise to a higher incidence of extrapyramidal
side effects than with oral medication – this occurs less with an atypical depot such as
Extrapyramidal side effects (mnemonic ADAPT)
Seen in
Acute Dystonia
Abnormal face and body movements, most common in
children and young adults.
Restlessness, with limbs in constant movement. May be
concealed by activity such as walking. Very poorly tolerated
by patients.
May be suppressed by antimuscarinic drugs
Rhythmic, involuntary movements of tongue, face and jaw.
May decrease upon drug cessation but may not – very socially
Dry mouth
Antimuscarinic Effects
Blurred vision
General cautions for Antipsychotics
 Elderly,
 Hepatic impairment
 Renal impairment
 Cardiovascular disease,
 Parkinson’s disease (may be
exacerbated by antipsychotics),
 Epilepsy (and conditions predisposing to
 Depression,
 Myasthenia gravis,
 Prostatic hypertrophy,
 Susceptibility to angle-closure glaucoma.
 Severe respiratory disease
 Patients with a history of jaundice or who
have blood dyscrasias
Urinary retention
General contraindications
 Comatose states,
 CNS depression
 Phaeochromocytoma.
 Most antipsychotics are best avoided
during pregnancy, unless essential.
 It is advisable to discontinue breastfeeding during treatment
Risperidone by Alan McLeod
Psychoses: 2 mg in 1–2 divided doses on first day then 4 mg in 1–2 divided doses on
second day (slower titration appropriate in some patients); usual dose range 4–6 mg daily;
doses above 10 mg daily only if benefit considered to outweigh risk (max. 16 mg daily);
Mania, initially 2 mg once daily, increased if necessary in steps of 1 mg daily; usual dose
range 1–6 mg daily;
Mode of operation:
 D2 receptor dopamine antagonist
 Also blocks 5-HT receptors
Side effects:
 Weight gain
 Extrapyramidal s/e at high doses (>6 mg)
 Postural hypotension
 Sedation (caution: driving, operating machinery etc)
 Dizziness
 Hyperglycemia +/- diabetes
 Hyperprolactinemia: galactorrhoea, gynaecomastia, amenorrhoea
 May lengthen QT interval
 Increased risk of stroke in elderly patients
with dementia
 Breast feeding
Cautions: Use with caution in:
 Elderly: assess CVS risk factors
 Hepatic impairment
 Renal impairment
 Pregnancy
 History of epilepsy
 CVS disease
 Obesity
 Parkinson’s
 Drugs which prolong QT interval
Effect of interaction
increased risk of ventricular arrhythmias when anti-
inhibitors, Alpha-blockers,
Angiotensin-II receptor antagonists
General anesthetic
Carbamazepine, Phenytoin,
valproate, barbiturates
arrhythmics that prolong the QT interval given with
antipsychotics that prolong the QT interval
Increased hypotensive effect
Increased sedation
Increased hypotensive effect
Reduces anti-seizure efficacy: seizure threshold
Increased tricyclic plasma concentration: ventricular
Monitoring: symptomatic monitoring, plus weight.
Olanzapine by Alan McLeod
 Schizophrenia,
 Mania / bipolar disorder
 Agitation / disturbed behaviour in schizophrenia / mania
 D2 receptor antagonist
 5HT receptor antagonist
Quetiapine by Alan McLeod
 Schizophrenia,
 Mania / bipolar disorder
 D1 / D2 receptor antagonist
 5HT1A / 5HT2 receptor antagonist
 H1 receptor antagonist (may be responsible for sedative effects)
Haloperidol by Alan McLeod
By mouth, initially 1.5–3 mg 2–3 times daily or 3–5 mg 2–3 times
 Schizophrenia
daily in severely affected or resistant patients; in resistant
 Other psychoses
schizophrenia up to 30 mg daily may be needed; adjusted
 Mania
according to response to lowest effective maintenance dose (as
 Short term management: low as 5–10 mg daily);
- Psychomotor agitation
By intramuscular or by intravenous injection, initially 2–10 mg,
- Excitement
then every 4–8 hours according to response to total max. 18 mg
- Violent / dangerously
daily; severely disturbed patients may require initial dose of up to
18 mg;
impulsive behaviour
 Severe anxiety (Short-term adjunctive management): by mouth, 500 micrograms BD
 Intractable hiccup: by mouth, 1.5 mg 3 times daily adjusted according to response;
 Nausea and vomiting: by mouth, 1 mg daily By IM or IV injection, 0.5–2 mg
As with all antipsychotics, it acts through blockage of dopamine receptors. It is
approximately 50 times more potent than chlorpromazine on a weight basis (50mg
chlorpromazine are equivalent to 1mg haloperidol). Haloperidol possesses a strong activity
against delusions and hallucinations, most likely due to an effective dopaminergic receptor
blockage in the mesocortex and the limbic system of the brain.
The peripheral antidopaminergic effects of haloperidol account for its strong antiemetic
activity. There, it acts at the chemoreceptor trigger zone (CTZ). Haloperidol is useful to treat
severe forms of nausea/emesis such as those resulting from chemotherapy. The peripheral
effects lead also to a relaxation of the gastric sphincter muscle and an increased release of
the hormone prolactin, with the possible emergence of breast enlargement and secretion of
milk (lactation) in both sexes.
As above plus
 subarachnoid haemorrhage
 metabolic disturbances such as hypokalaemia, hypocalcaemia, or hypomagnesaemia
Side effects
 pigmentation and photosensitivity reactions rare;
 extrapyramidal symptoms, particularly dystonic reactions and akathisia especially in
thyrotoxic patients;
 rarely weight loss;
 hypoglycaemia;
 inappropriate antidiuretic hormone secretion
Flupentixol by Alan McLeod
 D1 / D2 receptor antagonist; also antagonises 5HT receptors
 In decanoate ester form it can be given IM as a depot and lasts up to 4 weeks
 schizophrenia and other psychoses, particularly with apathy and withdrawal but not mania
or psychomotor hyperactivity (zuclopentixol may be used with mania / hyperactivity)
 depression
 Where a depot preparation is required to improve compliance
Chlorpromazine by Alan McLeod
‘Typical’ antipsychotic (in fact the first to be marketed!)
Indications & Dose
By mouth, initially 25 mg 3 times daily (or 75 mg at night),
 Schizophrenia
adjusted according to response, to usual maintenance dose
 Other psychoses
of 75–300 mg daily (but up to 1 g daily may be required in
 Mania
 Short term management: psychoses);
By intramuscular or by intravenous injection, 25–50 mg
- Severe anxiety
every 6–8 hours;
- Psychomotor agitation
By rectum in suppositories as chlorpromazine base
- Excitement
100 mg every 6–8 hours [unlicensed]
- Violent / dangerously
impulsive behaviour
 Intractable hiccup: by mouth, 25–50 mg 3–4 times daily
Mode of action: Central
Chlorpromazine acts as an antagonist of various postsynaptic receptors:
 Dopaminergic (subtypes D1, D2, D3 and D4, different antipsychotic properties on
productive and unproductive symptoms),
 Serotonergic (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive
properties as well as an attenuation of extrapyramidal side effects, but also leading to
weight gain, fall in blood pressure, sedation and ejaculation difficulties),
histaminergic (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and
weight gain),
alpha1/alpha2 (antisympathomimetic properties, lowering of blood pressure, reflex
tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual
dysfunction, but may also attenuate pseudoparkinsonism—controversial)
muscarinic (cholinergic) M1/M2 (causing anticholinergic symptoms like dry mouth,
blurred vision, constipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes
and loss of memory, but the anticholinergic action may attenuate extrapyramidal side
Additionally, chlorpromazine is a presynaptic inhibitor of dopamine reuptake, which
may lead to (mild) antidepressive and antiparkinsonian effects. This action could also
account for psychomotor agitation and amplification of psychosis (very rarely noted in
clinical use).
Mode of action: Peripheral
 Antagonist to H1 receptors (antiallergic effects), H2 receptors (reduction of forming of
gastric juice), M1/M2-receptors (dry mouth, reduction in forming of gastric juice) and
some 5-HT receptors (different anti-allergic/gastrointestinal actions).
 Because it acts on so many receptors, chlorpromazine is often referred to as a "dirty
Side effects:
As above (antipsychotics)
Hypnotics and their reversal agents
The pharmacological action of temazepam is thought to be the result of its
facilitating the action of gamma aminobutyric acid (GABA), an inhibitor
Diazepam is a benzodiazepine that binds to a specific subunit on the
GABAA receptor at a site that is distinct from the endogenous GABA
molecule.[5][6]The GABAA receptor is an inhibitory channel which, when
activated, decreases neurologic activity.
Due to the role of diazepam as a positive allosteric modulator of GABA,
when it binds to benzodiazepine receptors it causes inhibitory effects. This
arises from the hyperpolarization of the postsynaptic membrane, due to the
control exerted over negative chloride ions by GABAA receptors.[5][7]
Diazepam appears to act on areas of the limbic system, thalamus and
hypothalamus, inducing anxiolytic effects. Its actions are due to the
enhancement of GABA activity.[2][5]
Mood Stabilisers
Carbamazepine (Tegretol) by Ali Black
Voltage gated Na+ channels enable neurons to generate action potentials. After these
channels open to start the action potential, they inactivate, essentially closing the channel.
Carbamazepine stabilizes the inactivated state of sodium channels, meaning that fewer
channels are available to open, making brain cells less excitable.
A tricyclic-related compound, carbamazepine has a moderate anticholinergic action which is
responsible for some of its adverse effects. A tolerance may develop to the action of
carbamazepine after a few months
Indications: (see also: epilepsy drugs)
 Prophylaxis mania in manic depression where unresponsive to Lithium (may be used
alone or with Lithium)
 Treatment rapid cycling (>4 /yr) manic depression
 Trigeminal neuralgia
Prophylaxis of bipolar disorder: initially 100 mg daily in divided doses increased
until symptoms controlled; usual range 400–600 mg daily; max. 1.6 g daily
Serum levels: Aim for serum levels of 2-10mg/l: MEASURE until
established dose, then monitor.
Side effects:
NEURO: Drowsiness (start at low dose & gradually increase), dizzy, ataxia,
confusion, agitation, nystagmus, diplopia
SKIN: stevens-Johnson (erythema multiforme; very severe), rash
GI: anorexia and constipation, nausea, hepatotoxicity
OTHER: water intoxication - this can occur with high plasma levels and may cause
hyponatraemia, confusion and exacerbation of seizures (when treating epilepsy).
Pregnancy / breast-feeding: weigh up potential harm: benefit ratio
May be teratogenic!!! Spina bifida association.
Carbamazepine passes into breast milk in concentrations of about 25 to
60% of the plasma level. Affects of this have not been studied. Use with
Other contra-indications:
Previous bone marrow depression
hypersensitivity to the drug, or known sensitivity to any of the tricyclic
Recent (14 days) monoamine oxidase inhibitors use
REPORTED but are very rare. Routinely check FBC
Long-term toxicity studies in rats indicated a potential carcinogenic risk
Lithium Carbonate (Camcolit, Priadel) by Ali Black
Indications: Treatment and prophylaxis of mania. Can be used with Carbamazepine.
Agression, self-harm, recurrent depression.
Mechanism: Unclear. Probably increases serotonin transmission. Current hypotheses
include the interference with the phosphoinositide signalling pathway by either reducing
the synthesis of second messengers involved in the pathway or inhibiting inositol
monophosphatase activities; its neuroprotection against excitotoxicity caused by
glutamate hyperactivity; the suppression of intracellular calcium mobilization; its
stimulatory effect on ATP-dependent dopamine uptake; its regulation of gene
expression in long-term treatment; and the selective effect in G-protein subunit
expressions in brain cells.
Levels Required
Adjust to serum conc. to 0.4-1.0 mmol/l
Measure 12 hours post dose
Measure days 4-7 of first week treatment
Weekly till levelshave been acceptable and constant for 4 weeks
3 monthly thereafter.
Also check thyroid function (can cause hypothyroidism but impairing thyroxine release).
May require thyroxine
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