Re: Link to the ANCP report GSK admit to suicide attempts in clinical trials

January 25, 2004

GSK admit to ....suicide attempts ...in clinical trials of

adolescents with MDD

Suicidal thoughts and suicide attempts were mainly observed in

clinical trials of adolescents with Major Depressive Disorder).

PAXIL SEROXAT AROPAX

Paxil Seroxat Aropax

http://www.medsafe.govt.nz/DatasheetPage.htm

Adverse Events from Paediatric Clinical Trials

In paediatric clinical trials the following adverse events were

reported at a frequency of at least 2% of patients and occurred at a

rate at least twice that of placebo: decreased appetite, tremor,

sweating, hyperkinesia, hostility, agitation, emotional lability

(including crying, mood fluctuations, self-harm, suicidal thoughts

and attempted suicide. Suicidal thoughts and suicide attempts were

mainly observed in clinical trials of adolescents with Major

Depressive Disorder).

In studies that used a tapering regimen, symptoms reported during

the taper phase or upon discontinuation of paroxetine at a frequency

of at least 2% of patients and occurred at a rate at least twice

that of placebo were: nervousness, dizziness, nausea, emotional

lability and abdominal pain.

Data Sheet

AROPAX™ Tablets

Paroxetine

Presentation

AROPAX TABLETS: White, film coated, modified oval, biconvex tablets

containing 22.8mg paroxetine hydrochloride equivalent to 20mg

paroxetine free base.

The tablet has the product name and strength engraved on one side

and a breakline on the reverse to enable the tablets to be broken in

half if required.

Uses

Actions

Paroxetine is a potent and selective inhibitor of 5-

hydroxytryptamine (5-HT, serotonin) uptake and its antidepressant

action and effectiveness in the treatment of OCD and Panic Disorder

is thought to be related to its specific inhibition of 5-HT uptake

in brain neurones.

Paroxetine is chemically unrelated to the tricyclic, tetracyclic and

other available antidepressants.

Paroxetine has low affinity for muscarinic cholinergic receptors and

animal studies have indicated only weak anticholinergic properties.

In accordance with this selective action, in vitro studies have

indicated that, in contrast to tricyclic antidepressants, paroxetine

has little affinity for alpha1, alpha2 and beta-adrenoceptors,

dopamine (D2), 5-HT1 like, 5-HT2 and histamine (H1) receptors. This

lack of interaction with post-synaptic receptors in vitro is

substantiated by in vivo studies, which demonstrate lack of CNS

depressant and hypotensive properties.

Pharmacodynamic effects

Paroxetine does not impair psychomotor function and does not

potentiate the depressant effects of ethanol.

As with other selective 5-HT uptake inhibitors, paroxetine causes

symptoms of excessive 5-HT receptor stimulation when administered to

animals previously given monoamine oxidase (MAO) inhibitors or

tryptophan.

Behavioural and EEG studies indicate that paroxetine is weakly

activating at doses generally above those required to inhibit 5-HT

uptake. The activating properties are not " amphetamine-like " in

nature.

Animal studies indicate that paroxetine is well tolerated by the

cardiovascular system.

Paroxetine produces no clinically significant changes in blood

pressure, heart rate and ECG after administration to healthy

subjects.

Studies indicate that, in contrast to antidepressants, which inhibit

the uptake of nor-adrenaline, paroxetine has a much reduced

propensity to inhibit the antihypertensive effects of guanethidine.

Pharmacokinetics

Absorption

Paroxetine is well absorbed after oral dosing and undergoes first-

pass metabolism.

Due to first-pass metabolism, the amount of paroxetine available to

the systemic circulation is less than that absorbed from the

gastrointestinal tract. Partial saturation of the first-pass effect

and reduced plasma clearance occur as the body burden increases with

higher single doses or on multiple dosing. This results in

disproportionate increases in plasma concentrations of paroxetine

and hence pharmacokinetic parameters are not constant, resulting in

non-linear kinetics. However, the non-linearity is generally small

and is confined to those subjects who achieve low plasma levels at

low doses.

Steady state systemic levels are attained by 7-14 days after

starting treatment and pharmacokinetics do not appear to change

during long-term therapy.

Distribution

Paroxetine is extensively distributed into tissues and

pharmacokinetic calculations indicate that only 1% of the paroxetine

in the body resides in the plasma.

Approximately 95% of the paroxetine present in the plasma is protein

bound at therapeutic concentrations.

No correlation has been found between paroxetine plasma

concentrations and clinical effect (adverse experiences and

efficacy).

Transfer to human breast milk, and to the foetuses of laboratory

animals, occurs in small amounts.

Metabolism

The principal metabolites of paroxetine are polar and conjugated

products of oxidation and methylation which are readily cleared. In

view of their relative lack of pharmacological activity, it is most

unlikely that they contribute to paroxetine's therapeutic effects.

Metabolism does not compromise paroxetine's selective action on

neuronal 5-HT uptake.

Elimination

About 64% of the dose is excreted in the urine; urinary excretion of

unchanged paroxetine is generally less than 2% of the dose. About

36% of the dose is excreted in the faeces, probably via the bile;

faecal excretion of unchanged paroxetine represents less than 1% of

the dose. Thus paroxetine is eliminated almost entirely by

metabolism.

Metabolite excretion is biphasic, being initially a result of first-

pass metabolism and subsequently controlled by systemic elimination

of paroxetine.

The elimination half-life is variable but is generally about 1 day.

Special Patient Populations

Elderly and Renal/Hepatic Impairment

Increased plasma concentrations of paroxetine occur in elderly

subjects and in those subjects with severe renal and hepatic

impairment, but the range of plasma concentrations overlaps that of

healthy adult subjects.

Indications

Depression:

Depression of all types, including reactive and severe depression

and depression accompanied by anxiety.

AROPAX is indicated for the prevention of relapse and also

recurrence of further depressive episodes.

In the treatment of depressive disorders, AROPAX exhibits comparable

efficacy to standard antidepressants.

In general, improvement in patients starts after one week but does

not become superior to placebo until the second week of therapy.

AROPAX, in addition to its significant antidepressant effects, also

improves associated symptoms of anxiety.

There is also some evidence that AROPAX may be of therapeutic value

in patients who have failed to respond to standard therapy.

Morning dosing with AROPAX does not have any detrimental effect on

either the quality or duration of sleep. Moreover, patients are

likely to experience improved sleep as they respond to AROPAX

therapy.

Where it is clinical practice to co-prescribe short-acting hypnotics

with antidepressants, no additional adverse events have been

recorded.

AROPAX is effective in improving depression and suicidal ideation

concurrently during the first few weeks of therapy.

Long term treatment with AROPAX has shown that efficacy is

maintained for periods of at least one year.

Controlled clinical studies failed to demonstrate efficacy and do

not support the use of paroxetine in the treatment of children with

Major Depressive Disorder (see Adverse Effects).

Obsessive Compulsive Disorder:

AROPAX is indicated for the treatment of Obsessive Compulsive

Disorder (OCD).

In a placebo-controlled trial, the efficacy of AROPAX in the

treatment of OCD has been maintained for at least 1 year.

Panic Disorder:

AROPAX is indicated for the treatment of Panic Disorder with and

without agoraphobia.

The combination of AROPAX and cognitive-behavioural therapy has been

shown to be significantly more effective than cognitive-behavioural

therapy alone in the treatment of Panic Disorder.

In a placebo-controlled trial, the efficacy of AROPAX in the

treatment of Panic Disorder has been maintained for up to 1 year.

Social Anxiety Disorder/Social Phobia:

AROPAX has been shown to be effective in the treatment of Social

Anxiety Disorder/Social Phobia.

Generalised Anxiety Disorder:

AROPAX has been shown to be effective in the treatment of

Generalised Anxiety Disorder.

In a placebo-controlled trial, the efficacy of AROPAX in the

treatment of Generalised Anxiety Disorder has been maintained for up

to 32 weeks.

Posttraumatic Stress Disorder:

AROPAX has been shown to be effective in the treatment of

Posttraumatic Stress Disorder.

Dosage and Administration

It is recommended that paroxetine is administered once daily in the

morning with food. The tablet should be swallowed rather than chewed.

Depression:

The recommended dose is 20mg daily. Some patients not responding to

a 20mg dose may benefit from dose increases, in 10mg/day increments,

up to a maximum of 50mg/day. It is recommended that AROPAX is

administered once daily with food. Based on observed beneficial

effects on sleep it is recommended that the dose be taken in the

morning. If, however, a patient experiences unacceptable daytime

somnolence with AROPAX, consideration should be given to dosing at

bedtime. The tablet should be swallowed rather than chewed.

As with all antidepressant drugs, dosage should be reviewed and

adjusted if necessary within 2 to 3 weeks of initiation of therapy

and thereafter as judged clinically appropriate. Dose changes should

occur at intervals of at least one week.

Patients with depression should be treated for a sufficient period

to ensure that they are free from symptoms. This period may be

several months.

Controlled clinical studies in children aged 7 to 17 years failed to

demonstrate efficacy and do not support the use of paroxetine in the

treatment of children with Major Depressive Disorder (see Adverse

Effects).

Obsessive Compulsive Disorder:

The recommended dose is 40mg (2 tablets) daily. Patients should

start on 20mg and the dose can be increased weekly in 10mg

increments. Some patients will benefit from having their dose

increased up to a maximum of 60mg/day.

It is recommended that AROPAX is administered once daily with food.

The tablet should be swallowed rather than chewed.

Patients with OCD should be treated for a sufficient period to

ensure that they are free from symptoms. This period may be several

months or even longer.

Panic Disorder:

The recommended dose is 40mg daily. Patients should be started on

10mg/day and the dose increased weekly in 10mg increments according

to patient's response. Some patients may benefit from having their

dose increased up to a maximum of 60mg/day.

A low initial starting dose is recommended to minimise the potential

worsening of panic symptomatology, which is generally recognised to

occur early in the treatment of this disorder.

Patients with panic disorder should be treated for a sufficient

period to ensure that they are free from symptoms. This period may

be several months or even longer.

Social Anxiety Disorder/Social Phobia:

The recommended dose is 20mg daily. Some patients not responding to

a 20mg dose may benefit from having dose increases in 10mg

increments as required, up to a maximum of 50mg/day according to the

patient's response.

Generalised Anxiety Disorder:

The recommended dose is 20mg daily. Some patients not responding to

a 20mg dose may benefit from having dose increases in 10mg

increments as required, up to a maximum of 50mg/day according to the

patient's response.

Posttraumatic Stress Disorder:

For the majority of patients, the recommended starting and

maintenance dose is 20mg daily. However, some patients not

responding to a 20mg dose may benefit from having dose increases in

10mg increments as required, up to a maximum of 50mg/day according

to the patient's response.

The use of AROPAX beyond 12 weeks has not been investigated in

clinical trials.

Populations

Elderly: Increased plasma concentrations of AROPAX occur in elderly

subjects, but the range of concentrations overlaps with that

observed in younger subjects.

Children: The efficacy of paroxetine in children under the age of 18

years has not been established. Controlled clinical studies in

depression failed to demonstrate efficacy and do not support the use

of paroxetine in the treatment of children under the age of 18 years

with depression (see Adverse Effects).

Renal/Hepatic Impairment: Increased plasma concentrations of AROPAX

occur in patients with severe renal impairment (creatinine clearance

<30mL/min) or hepatic impairment. Therefore, dosage should be

restricted to the lower end of the dosage range.

Discontinuation Of Paroxetine

As with other psychoactive medications, abrupt discontinuation

should generally be avoided (see Warnings and Precautions & Adverse

Effects sections). The taper phase regimen used in recent clinical

trials involved an incremental decrease in the daily dose by 10

mg/day at weekly intervals. When a daily dose of 20 mg/day was

reached, patients were continued on this dose for one week before

treatment was stopped. If intolerable symptoms occur following a

decrease in the dose or upon discontinuation of treatment, then

resuming the previously prescribed dose may be considered.

Subsequently, the physician may continue decreasing the dose, but at

a more gradual rate.

Contraindications

Known hypersensitivity to paroxetine and excipients.

Paroxetine should not be used in combination with monoamine oxidase

(MAO) inhibitors or within 2 weeks of terminating treatment with MAO

inhibitors. Likewise, MAO inhibitors should not be introduced within

2 weeks of cessation of therapy with paroxetine (see Interactions)

Paroxetine should not be used in combination with thioridazine,

because, as with other drugs, which inhibit the hepatic enzyme

CYP450 2D6, paroxetine can elevate plasma levels of thioridazine

(see Interactions). Administration of thioridazine alone can lead to

QTc interval prolongation with associated serious ventricular

arrhythmia such as torsades de pointes, and sudden death.

Warnings and Precautions

MAO INHIBITORS: Treatment with paroxetine should be initiated

cautiously at least 2 weeks after terminating treatment with MAO

inhibitors and dosage of paroxetine should be increased gradually

until optimal response is reached (see Contraindications and

Interactions).

As with other SSRI's, paroxetine should be used with caution in

patients already receiving neuroleptics, since symptoms suggestive

of Neuroleptic Malignant Syndrome cases have been reported with this

combination.

MANIA: As with all antidepressants, paroxetine should be used with

caution in patients with a history of mania.

TRYPTOPHAN: As adverse experiences have been reported when

tryptophan was administered with another selective 5-HT re-uptake

inhibitor, paroxetine should not be used in combination with

tryptophan medication. (See Interactions).

CARDIAC CONDITIONS: The usual precautions should be observed in

patients with cardiac conditions.

EPILEPSY: As with other antidepressants, paroxetine should be used

with caution in patients with epilepsy.

SEIZURES: Overall the incidence of seizures is less than 0.1% in

patients treated with paroxetine.

Paroxetine should be discontinued in any patient who develops

seizures.

SUICIDE/SUICIDAL IDEATION AND PSYCHIATRIC DISORDERS: The possibility

of a suicide attempt is an inherent component of major depressive

disorder and may persist until significant remission occurs. As

improvement may not occur during the first few weeks or more of

treatment, patients should be closely monitored until such

improvement occurs. Other psychiatric conditions for which

paroxetine is prescribed can also be associated with an increased

risk of suicidal behaviour. In addition, these conditions may be co-

morbid with major depressive disorder. The same precautions observed

when treating patients with major depressive disorder should

therefore be observed when treating patients with other psychiatric

disorders.

ECT: There is little clinical experience of the concurrent

administration of paroxetine with ECT.

GLAUCOMA: As with other SSRI's, paroxetine infrequently causes

mydriasis and should be used with caution in patients with narrow

angle glaucoma.

Hyponatraemia has been reported rarely, predominantly in the

elderly. The hyponatraemia generally reverses on discontinuation of

paroxetine.

Skin and mucous membrane bleedings have been reported following

treatment with paroxetine. Paroxetine should therefore be used with

caution in patients concomitantly treated with drugs that give an

increased risk for bleeding, and in patients with a known tendency

for bleeding or those with predisposing conditions.

SYMPTOMS SEEN ON DISCONTINUATION OF PAROXETINE TREATMENT: Some

patients may experience symptoms on discontinuation of paroxetine,

particularly if treatment is stopped abruptly (see Adverse Effects).

It is therefore advised that the dose should be gradually tapered

when discontinuing treatment (see Dosage and Administration).

Pregnancy and Lactation

Although animal studies have not shown any teratogenic or selective

embryotoxic effects, the safety of paroxetine in human pregnancy has

not been established and it should not be used during pregnancy or

by nursing mothers unless the potential benefit outweighs the

possible risk.

Effects on Ability to Drive and Use Machines

Clinical experience has shown that therapy with paroxetine is not

associated with impairment of cognitive or psychomotor function.

However, as with all psychoactive drugs, patients should be

cautioned about their ability to drive a car and operate machinery.

Although paroxetine does not increase the mental and motor skill

impairments caused by alcohol, the concomitant use of paroxetine and

alcohol is not advised.

Other: Preclinical Safety Data

Toxicology studies have been conducted in rhesus monkeys and albino

rats; in both, the metabolic pathway is similar to that described

for humans. As expected with lipophilic amines, including tricyclic

antidepressants, phospholipidosis was detected in rats.

Phospholipidosis was not observed in primate studies of up to one

year duration at doses that were 6 times higher than the recommended

range of clinical doses.

Carcinogenesis: In two-year studies conducted in mice and rats,

paroxetine had no tumorigenic effect.

Genotoxicity: Genotoxicity was not observed in a battery of in vitro

and in vivo tests.

Adverse Effects

Some of the adverse experiences listed below may decrease in

intensity and frequency with continued treatment and do not

generally lead to cessation of therapy. Adverse drug reactions are

listed below by system organ class and frequency. Frequencies are

defined as: very common (= 1/10), common (= 1/100, <1/10), uncommon

(= 1/1,000, <1/100), rare (= 1/10,000, <1/1,000), very rare

(<1/10,000), including isolated reports. The frequencies of common

and uncommon events were generally determined from pooled safety

data from a clinical trial population of >8000 paroxetine-treated

patients and are quoted as excess incidence over placebo. Rare and

very rare events were generally determined from post-marketing data

and refer to reporting rate rather than true frequency.

Blood & lymphatic system disorders

Uncommon: abnormal bleeding, predominantly of the skin and mucous

membranes (mostly ecchymosis).

Very rare: thrombocytopenia.

Immune system disorders

Very rare: allergic reactions (including urticaria and angioedema).

Endocrine disorders

Very rare: syndrome of inappropriate anti-diuretic hormone secretion

(SIADH).

Metabolism & nutrition disorders

Common: decreased appetite.

Rare: hyponatraemia.

Hyponatraemia has been reported predominantly in elderly patients

and is sometimes due to syndrome of inappropriate anti-diuretic

hormone secretion (SIADH).

Psychiatric disorders

Common: somnolence, insomnia.

Uncommon: confusion.

Rare: manic reactions.

Nervous system disorders

Common: dizziness, tremor.

Uncommon: extrapyramidal disorders.

Rare: convulsions.

Very rare: serotonin syndrome (symptoms may include agitation,

confusion, diaphoresis, hallucinations, hyperreflexia, myoclonus,

shivering tachycardia and tremor).

Reports of extrapyramidal disorders including oro-facial dystonia

have been received in patients sometimes with underlying movement

disorders or who were using neuroleptic medication. In addition,

akathisia has been rarely reported.

Eye disorders

Common: blurred vision.

Very rare: acute glaucoma.

Cardiac disorders

Uncommon: sinus tachycardia

Vascular disorders

Uncommon: transient increases or decreases in blood pressure.

Transient increases or decreases of blood pressure have been

reported following treatment with paroxetine, usually in patients

with pre-existing hypertension or anxiety.

Respiratory, thoracic and mediastinal disorders

Common: yawning.

Gastrointestinal disorders

Very common: nausea.

Common: constipation, diarrhoea, dry mouth.

Hepato-biliary disorders

Rare: elevation of hepatic enzymes.

Very rare: hepatic events (such as hepatitis, sometimes associated

with jaundice and/or liver failure).

Elevation of hepatic enzymes has been reported. Post-marketing

reports of hepatic events (such as hepatitis, sometimes associated

with jaundice, and/or liver failure) have also been received very

rarely. Discontinuation of paroxetine should be considered if there

is prolonged elevation of liver function test results.

Skin & subcutaneous tissue disorders

Common: sweating.

Uncommon: skin rashes.

Very rare: photosensitivity reactions.

Renal & urinary disorders

Uncommon: urinary retention.

Reproductive system & breast disorders

Very common: sexual dysfunction.

Rare: hyperprolactinaemia / galactorrhoea.

General disorders & administration site conditions

Common: asthenia.

Very rare: peripheral oedema.

Symptoms seen on discontinuation of paroxetine treatment

Common: Dizziness, sensory disturbances, sleep disturbances, anxiety.

Uncommon: Agitation, nausea, sweating.

As with many psychoactive medicines, discontinuation of paroxetine

(particularly when abrupt) may lead to symptoms such as dizziness,

sensory disturbances (including paraesthesia and electric shock

sensations), sleep disturbances, agitation or anxiety, nausea and

sweating. In the majority of patients, these events are mild to

moderate and are self-limiting. No particular patient group appears

to be at higher risk of these symptoms; it is therefore advised that

when paroxetine treatment is no longer required, gradual

discontinuation by dose tapering be carried out (see Dosage and

Administration & Warnings and Precautions).

Adverse Events from Paediatric Clinical Trials

In paediatric clinical trials the following adverse events were

reported at a frequency of at least 2% of patients and occurred at a

rate at least twice that of placebo: decreased appetite, tremor,

sweating, hyperkinesia, hostility, agitation, emotional lability

(including crying, mood fluctuations, self-harm, suicidal thoughts

and attempted suicide. Suicidal thoughts and suicide attempts were

mainly observed in clinical trials of adolescents with Major

Depressive Disorder).

In studies that used a tapering regimen, symptoms reported during

the taper phase or upon discontinuation of paroxetine at a frequency

of at least 2% of patients and occurred at a rate at least twice

that of placebo were: nervousness, dizziness, nausea, emotional

lability and abdominal pain.

Interactions

Interactive Effects on Paroxetine

Clinical studies have shown the absorption and pharmacokinetics of

paroxetine to be unaffected or only marginally affected (i.e. at a

level which warrants no change in dosing regimen) by:

food

antacids

digoxin

propranolol

alcohol: paroxetine does not increase the impairment of mental and

motor skills caused by alcohol, however, the concomitant use of

paroxetine and alcohol is not advised.

lithium: although there is no PK interaction, since there is limited

experience in patients, the concurrent administration of paroxetine

and lithium should be undertaken with caution.

drug metabolising enzymes

The metabolism and pharmacokinetics of paroxetine may be affected by

the induction or inhibition of drug metabolising enzymes. For

example, cimetidine, a known drug metabolising enzyme inhibitor can

increase the bioavailability of paroxetine.

When paroxetine is to be co-administered with a known drug

metabolising enzyme inhibitor (eg sodium valproate), consideration

should be given to using doses at the lower end of the range.

No initial dosage adjustment is considered necessary when the drug

is to be co-administered with known drug metabolising enzyme

inducers (e.g. carbamazepine, phenytoin). Any subsequent dosage

adjustment should be guided by clinical effect (tolerability and

efficacy).

Interactive Effects of Paroxetine on Other Drugs

Daily administration of paroxetine increases significantly the

plasma levels of procyclidine. If anticholinergic effects are seen,

the dose of procyclidine should be reduced.

anticonvulsants: carbamazepine, phenytoin, sodium valproate.

Concomitant administration showed no effect on

pharmacokinetic/dynamic profile in epileptic patients.

P450 isoenzymes

CYP2D6: As with other antidepressants, including other SSRIs,

paroxetine inhibits the hepatic cytochrome P450 enzyme CYP2D6.

Inhibition of CYP2D6 may lead to increased plasma concentrations of

co-administered drugs metabolised by this enzyme. These include

certain tricyclic antidepressants (e.g. amitriptyline,

nortriptyline, imipramine and desipramine), phenothiazine

neuroleptics (e.g. perphenazine and thioridazine), risperidone, Type

1c antiarrhythmics (e.g. propafenone and flecainide) and metoprolol.

CYP3A4: An in vivo interaction study involving the co-administration

under steady state conditions of paroxetine and terfenadine, a

substrate for cytochrome CYP3A4, revealed no effect of paroxetine on

terfenadine pharmacokinetics. A similar in vivo interaction study

revealed no effect of paroxetine on alprazolam pharmacokinetics and

vice-versa. Concurrent administration of paroxetine with

terfenadine, alprazolam and other drugs that are CYP3A4 substrates

would not be expected to cause a hazard.

SSRI Class Interactions

As with other SSRIs, co-administration with serotonergic drugs [e.g.

MAO inhibitors (see Contraindications), L-tryptophan] may lead to an

incidence of 5HT associated effects (Serotonergic Syndrome; see

Adverse Effects). The risk of using paroxetine in combination with

other CNS active drugs has not been systematically evaluated.

Consequently caution is advised if concomitant administration is

required.

Overdosage

Symptoms and Signs

A wide margin of safety is evident from available overdose

information on paroxetine.

Experience of paroxetine in overdose has indicated that, in addition

to those symptoms mentioned under " Adverse effects " , vomiting,

dilated pupils, fever, blood pressure changes, headache, involuntary

muscle contractions, agitation, anxiety and tachycardia have been

reported.

Patients have generally recovered without serious sequelae even when

doses of up to 2000mg have been taken alone. Events such as coma or

ECG changes have occasionally been reported and, very rarely a fatal

outcome, but generally when paroxetine was taken in conjunction with

other psychotropic drugs, with or without alcohol.

Treatment

No specific antidote is known.

The treatment should consist of those general measures employed in

the management of overdose with any antidepressant. Where

appropriate, the stomach should be emptied either by the induction

of emesis, lavage or both. Following evacuation, 20 to 30g of

activated charcoal may be administered every 4 to 6 hours during the

first 24 hours after ingestion. Supportive care with frequent

monitoring of vital signs and careful observation is indicated.

Pharmaceutical Precautions

Incompatibilities

There are no known incompatibilities with paroxetine tablets. The

tablet should be swallowed whole, not chewed.

Shelf Life

2 years when stored below 30°C.

Special Precautions for Storage

Tablets: Store in a dry place at a temperature not exceeding 30°C.

Medicines Classification

Prescription Only Medicine

Package Quantities

AROPAX, 20mg: 30 tablet packs (blisters in strips containing 10

tablets).

Name and Address

GlaxoKline NZ Limited

Quay Tower

Cnr Albert & Customs Streets

Private Bag 106600

Downtown Auckland

NEW ZEALAND

Phone: (09) 367 2900

Facsimile: (09) 367 2506

Date of Preparation

Issue number: 17

Issue date: 5 June 2003

AROPAX™ is a trademark of the GlaxoKline group of companies.

Ref: MDS Version 023

> Hi, I'm new. I haven't read much of the board yet, but I thought

I

> would post the link to the ACNP Task Force " PRELIMINARY REPORT OF

THE

> TASK FORCE ON SSRIs AND SUICIDAL BEHAVIOR IN YOUTH "

>

> http://www.acnp.org/exec_summary.pdf

>

> Please note that members of the task force are also the

researchers

> who did some of the original studies that were reviewed. Also

check

> the drug company connections of the task force members listed in

the

> final pages.

>

> I would also like to point out the the single most effective and

> safest treatment for depression has consistently been proven by

the

> drug companies clinical double blind studies to be the placebo.

In

> most (all?) cases, the studied medication out perform the placebo

by

> less than 20%, often in the 5-10% range while the improvement rate

for

> the placebo was consistently above 35%, in at least one case as

high

> as 60%. The more the researchers refine the definition of

improvement

> in depressive symptoms so that the drug scores higher, the placebo

> also scores higher.

January 25, 2004