Psychiatric Drugs 2005 Book, Psychologia po angielsku

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Handbook of Psychiatric Drugs
2005 Edition
Lawrence J. Albers, MD
Associate Clinical Professor
Department of Psychiatry and Human Behavior
University of California, Irvine, College of Medicine
Rhoda K Hahn, MD
Christopher Reist, MD
Associate Professor and Vice Chair
Department of Psychiatry and Human Behavior
University of California, Irvine, College of Medicine
Current Clinical Strategies Publishing
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Copyright © 2005 by Current Clinical Strategies Publishing. All
rights reserved. This book, or any parts thereof, may not be repro-
duced or stored on a network without the permission of the pub-
lisher. The reader is advised to consult the drug package insert and
other references before using any therapeutic agent. No warranty
exists, expressed or implied, for errors and omissions in this text.
Current Clinical Strategies is a registered trademark of Current
Clinical Strategies Publishing Inc.
Current Clinical Strategies Publishing
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Internet: www.ccspublishing.com/ccs
Indications for medications contained in this book sometimes may
not be approved by the FDA. Varying degrees of empirical evidence
exist for the effectiveness of medications for non- FDA approved
uses. The authors have included those off-label indications where
sufficient research has been completed to warrant the consideration
of these agents as treatment alternatives.
Printed in USA
ISBN 1929622-61-9
 Antidepressants
Serotonin-Specific Reuptake Inhibitors
I. Indications
A.
Serotonin-Specific Reuptake Inhibitors (SSRIs) are the most
widely prescribed class of antidepressants. SSRIs have
proven efficacy in the treatment of major depression,
dysthymia, obsessive-compulsive disorder (OCD), panic
disorder, bulimia nervosa, post-traumatic stress disorder,
generalized anxiety disorder and social phobia (social anxiety
disorder).
B.
SSRIs are also effective in the treatment of bipolar depression
and premenstrual dysphoric disorder. These agents have
some efficacy in the treatment of pain syndromes, such as
migraine headaches and chronic pain, but appear to be less
effective than tricyclics. There is some evidence that they be
effective in impulse control disorders. These agents have also
been used to treat borderline personality disorder.
II. Pharmacology
A.
SSRIs block serotonin reuptake into presynaptic nerve
terminals, leading to enhanced serotonergic
neurotransmission.
B.
The half-life for most of these agents is approximately 24
hours for the parent compound. Fluoxetine, however, has a
half-life of 2-4 days, and the active metabolite of fluoxetine,
norfluoxetine, has a 7- to 10-day half-life. Thus, fluoxetine
requires over a month to reach steady-state plasma concen-
trations while the other SSRIs take approximately 5 days.
C.
With the exception of escitalopram and fluvoxamine, the
SSRIs are highly bound to plasma proteins. SSRIs have
significantly less effect on muscarinic, histaminic, and
adrenergic receptors, compared to tricyclic antidepressants
(TCAs), and the SSRIs are better tolerated.
III.Clinical Guidelines
A. Dosage:
SSRIs have the advantage of once-daily dosing. The
dosage of fluoxetine, citalopram, and paroxetine is 20 mg per
day; the dosage should be decreased to 10 mg per day in the
elderly. The initial dose of escitalopram is 10 mg/day.
Sertraline and fluvoxamine are dosed at 50 mg per day, but
the dosage is decreased to 25 mg per day in elderly patients.
There is no linear relationship between the SSRI dose and the
response. For many patients, the dosage does not need to be
increased.
B. Obsessive-Compulsive Disorder and Bulimia:
Higher
dosages of SSRIs, such as 60-80 mg of fluoxetine or 200-300
mg of sertraline, have been used to treat obsessive-compul-
sive disorder and bulimia. While high doses may be neces-
sary in some patients, many patients will respond to standard
dosing after 6-12 weeks. When greater than 40 mg a day of
fluoxetine is given, the dosage should be divided into two
doses to minimize side effects.
C. Panic Disorder:
Patients with panic disorder should be
started at a low dosage to prevent increased anxiety in the
initial weeks of treatment. Patients should start at 12.5- 25 mg
of sertraline, 5-10 mg of paroxetine, 10-20 mg of citalopram,
5 mg of escitalopram, or 5 mg of fluoxetine. After 1-3 weeks,
the dosage may be increased gradually to standard dosages.
D. Response Time:
SSRIs require 2-4 weeks to begin to
alleviate symptoms of depression, and treatment should
continue for 6-8 weeks before a patient is considered non-
responsive to treatment.
E. Plasma Levels:
There is no correlation between plasma
concentrations of SSRIs and clinical efficacy. Measuring
plasma levels is not clinically indicated.
F. Safety:
SSRIs are much safer in overdose than other antide-
pressants, such as TCAs or MAOIs (monoamine oxidase
inhibitors).
G. Suicidality:
Beginning in 2003, regulatory agencies in the US
and the UK began issuing concerns about antidepressant use
in children and adolescents.
IV. Adverse Drug Reactions
A. Tolerability:
SSRIs are better tolerated than TCAs or MAOIs.
1. Alpha-1 Blockade:
SSRIs do not produce orthostatic
hypotension because they do not block alpha-1-adrenergic
receptors like tricyclic agents.
2. Histamine Blockade:
SSRIs produce markedly less
sedation or weight gain than TCAs or MAOIs because of
minimal effect on histamine receptors.
3. Muscarinic Blockade:
SSRIs usually do not cause dry
mouth, constipation, blurred vision, or urinary retention
because they have minimal effect on muscarinic
cholinergic receptors.
4. Seizures:
SSRIs have a seizure rate of approximately
0.2%, which is slightly lower than the rate for TCAs.
B. Side Effects:
The side effects of SSRIs are primarily medi-
ated by their interaction with serotonergic neurotransmission:
1. Gastrointestinal effects,
such as nausea and diarrhea,
are the most common adverse reactions. Nausea usually
improves after the first few days of treatment. Giving the
medication with food often alleviates the nausea.
2. Decreased appetite
is common early in treatment be-
cause of nausea, and this problem usually improves after
several days.
3. Headaches
(usually transient) occur occasionally upon
initiation of treatment. In some patients, headaches are
persistent.
4. Insomnia
may occur with any of the SSRIs, but it is more
common with fluoxetine and sertraline. Insomnia usually
responds to treatment with trazodone 50-100 mg qhs. The
SSRI should be given in the morning if insomnia occurs.
5.
SSRIs are less sedating than tricyclic antidepressants, but
sedation can occur with paroxetine or fluvoxamine. If
sedation occurs, the medication should be given at bed-
time.
6.
Sexual dysfunction such as decreased libido, erectile
dysfunction, delayed ejaculation and anorgasmia can
occur, and this problem may be treated with Sildenafil
(Viagra) 50-100 mg taken one hour before sex, tadalafil
(Cialis) 5-20 mg prior to sexual activity, vardenafil (Levitra)
5-20 mg one hour before sex, bupropion (Wellbutrin) 75-
150 mg bid, buspirone (BuSpar) 5-20 mg bid-tid,
mirtazapine 15-30 mg one hour before sex, nefazodone
100 mg one hour before sex or switching the antidepres-
sant to bupropion, nefazodone or mirtazapine.
7.
Serotonin syndrome, characterized by nausea, confusion,
hyperthermia, autonomic instability, tremor, myoclonus,
rigidity, seizures, coma and death, can occur when SSRIs
are combined with MAOIs. SSRIs should not be used for 2
weeks before or after the use of an MAOI. For fluoxetine,
5-6 weeks should elapse after discontinuation of the MAOI
because of its long half-life.
C. Miscellaneous Side Effects:
SSRIs may also cause sweat-
ing, anxiety, dizziness, tremors, fatigue, and dry mouth.
D. Mania:
SSRIs, like all other antidepressants, can induce
mania or rapid cycling in bipolar patients. However, the
tricyclics are more likely to induce mania than SSRIs.
E. SSRI Discontinuation Syndrome
: On discontinuation, some
patients may experience dizziness, lethargy, nausea, irritabil-
ity, and headaches. These symptoms are usually transient
and are more likely to occur with short-acting agents, such as
paroxetine and fluvoxamine. These symptoms can be
prevented by slowly tapering the medication over several
weeks when discontinuing the drug. Discontinuation of
paroxetine may be complicated by cholinergic rebound
symptoms, such as diarrhea.
F. Restlessness:
An akathisia-like syndrome has been reported
with fluoxetine. Akathisia can be treated by reducing the dose
of the SSRI. Agitation can be profound and often requires
discontinuation of the medication.
G. Teratogenic Effects:
All SSRIs are pregnancy category C.
However, there is no evidence that SSRIs cause major birth
defects. The impact of untreated depression on the mother
and fetus must be considered when determining these risk-
benefit decisions.
H. Breast Feeding:
SSRIs are secreted into breast milk in
minute amounts. A careful discussion of the risk-benefit ratio
should occur prior to breastfeeding.
V. Drug Interactions
A. Cytochrome P450 Enzymes:
SSRIs are competitive inhibi-
tors of a variety of cytochrome P450 liver enzymes. This can
result in elevated plasma levels of medications metabolized
by these enzymes. Elevated plasma levels may lead to toxic
side effects.
B. Potential Toxicity:
Toxic side effects of desipramine can be
seen when it is given concomitantly with SSRIs, such as
fluoxetine and paroxetine. Desipramine is metabolized by the
liver enzyme cytochrome P4502D6 (CYP2D6) and fluoxetine
is a potent inhibitor of cytochrome CYP2D6. Fluoxetine can
elevate plasma desipramine levels up to 400%, with subse-
quent increased sedation, anticholinergic effects, tremors and
potential increased risk of seizures or cardiotoxicity.
C. Substrates/Inhibitors
1.
Table 1 lists the substrates of several P450 liver enzymes,
and table 2 indicates the degree of inhibition of the en-
zymes by each SSRI. The greater the inhibition, the greater
the likelihood of a drug-drug interaction.
2.
Drugs that have a narrow therapeutic index are more likely
to produce toxic symptoms when combined with a strong
inhibitor of their metabolism. Drugs with a narrow therapeu-
tic index include antiarrhythmics, anticonvulsants, warfarin,
and theophylline.
D. Warfarin:
SSRIs may increase levels of warfarin via P450
interactions and competition for plasma protein binding sites.
Prothrombin times should be carefully monitored when
initiating SSRIs in a patient on warfarin.
 Table 1. Substrates of the P450 Enzymes
CYP1A
2
Acetaminophen
Amitriptyline
Caffeine
Clomipramine
Clozapine
Cyclobenzaprine
Dacarbazine
Flutamide
Fluvoxamine
Grepafloxen
Haloperidol
Imipramine
Mexiletine
Mirtazapine
Methadone
Odansetron
Olanzapine
Paracetamol
Pentoxifylline
Phenacetin
Propranolol
R-Warfarin
Ropinorole
Tacrine
Theophylline
Thioridazine
Thiothixene
CYP2D
6
Amitriptyline
Amphetamine
Bufaralol
Benztropine
Clomipramine
Clozapine
Codeine
Debrisoquine
Desipramine
Dextromethorph
an Diltiazem
Donepezil
Encainide
Ethylmorphine
Flecainide
Haloperidol
Hydrocodone
Imipramine
MCPP
Metoprolol
Mexiletine
Mirtazapine
Molindone
Nortriptyline
Odansetron
Oxycodone
Paroxetine
Perhexiline
Perphenazine
Propafenone
Propranolol
Quinidine
Quetiapine
Risperidone
Sertraline
Sparteine
Tamoxifen
Thioridazine
Timolol
Trazodone
Tramadol
Venlafaxine
CYP2C
9
Carmustine
Celecoxib
Diclofenac
Glyburide
Glypizide
Ibuprofen
Indomethacin
Losartan
Mefenamic
acid
Naproxen
Phenytoin
Piroxicam
Paclitaxel
Rosiglitazone
S-Warfarin
Suprofen
Tamoxifen
Tetrahydrocannibi
nol
Tolbutamide
Torsemide
Valsartan
CYP2C
19
Amitriptyline
Citalopram
Clomipramine
Cyclophosphami
de
Diazepam
Hexobarbital
Imipramine
Lansoprazole
Mephebarbita
l
Mephenytoin
Moclobemide
Omeprazole
Pantoprazole
Proguanil
Propranolol
Rabeprazole
Teniposide
CYP3A
4
Acetaminophen
Alfentanil
Alprazolam
Amiodarone
Amitriptyline
Amlodipine
Amprenavir
Avorstatin
Azithromycin
Bromocriptine
Bulsulfan
Buspirone
Carbamazepine
Carvedilol
Cerivastatin
Chlordiazepoxid
e
Chloroquine
Ciprofloxacin
Cilostazol
Cisapride
Citalopram
Clarithromycin
Clomipramine
Clonazepam
Clozapine
Cortisol
Cyclobenzaprine
Cyclosporine
Cyclophosphami
de Dapsone
Danorubicin
Delaviridine
Dexamethasone
Diazepam
Diltiazem
Dirithromycin
Dirithromycin
Disopyramide
Donepezil
Efavirenz
Ergots
Erythromycin
Estradiol
Estrogen
Ethosuximide
Etoposide
Felodipine
Fentanyl
Imipramine
Indinavir
Isofamide
Ketoconazole
Lansoprazole
Mirtazapine
Lidocaine
Lopinavir
Loratadine
Lovastatin
Metoprolol
Midazolam
Nefazodone
Nevirapine
Nicardipine
Nifedipine
Nimodipine
Nisoldipine
Nitrendipine
Odansetron
Omeprazole
Pantoprazole
Paclitaxel
Pergolide
Propafenone
Primaquine
Progesterone
Quetiapine
Quinidine
Rabeprazole
Rapamycin
Rifabutin
Rifampin
Rokitamycin
Ropinirole
Saquinous
Siburtramine
Sildenafil
Simvastatin
Tacrolimus
Tamoxifen
Temazepam
Tenoposide Tes-
tosterone
Tiagabine
Toremifene
Trazodone
Triazolam
Trofosfamide
Troleandomycin
Valproate
Verapamil
Vesnarinone
Vinblastine
Vincristine
Vindesine
Vinorelbin
Zaleplon
Zolpidem
Table 2.
Degree of inhibition of Cytochrome P450 En-
zymes by SSRIs
1A2
2C9
2C19
2D6
3A4
Escitalo-
pram
(Lexapro)
0/+
0/+
0/+
+
0/+
Citalopram
(Celexa)
0/+
0/+
0/+
+
0/+
Fluoxetine
(Prozac)
0/+
++/+++
++/++
+
++++
+/++
Fluvoxam-
ine (Lu-
Vox)
++++
0/+
++++
0/+
+++
Paroxetine
(Paxil)
0/+
0/+
0/+
++++
0/+
Sertraline
(Zoloft)
0/+
0/+
+/++
+
0/+
Citalopram (Celexa)
I. Indications:
Effective for a variety of depressive and anxiety
disorders.
Preparations:
10, 20 and 40 mg (20 mg and 40 mg tablets are
scored). Oral suspension: 10 mg/5 mL.
II. Dosage:
Depression:
20 mg per day, usually given at bedtime. The
dosage may be increased to 40 mg per day after one week.
Maximum dosage is 60 mg/day, and this dosage should be
reserved for treatment refractory patients who have had a 4- to
6-week trial at 40 mg/day.
Elderly:
10 mg per day for one week, then increase to 20
mg/day. Treatment refractory patients may require 40 mg/day
after a trial of 4-6 weeks on 20 mg/day.
III. Half-Life: 35 hr.
IV. Clinical Guidelines:
Citalopram has low overall effects on P450
enzymes (see table 2).
V. Drug Interactions:
Cytochrome P450: Modest inhibition of the
hepatic enzyme, CYP2D6, may lead to mild elevations of TCAs
and antiarrhythmics (see Tables 1 & 2). This interaction is
unlikely to be clinically significant,
Escitalopram (Lexapro)
I. Indications:
Effective for a variety of depressive and anxiety
disorders.
Preparations:
5 mg (unscored), 10 and 20 mg scored tablets.
Oral solution:
5 mg/5 mL.
II. Dosage:
Depression:
10 mg per day. The dosage may be increased to
20 mg per day after one week. Maximum dosage is 30 mg/day,
and this dosage should be reserved for treatment refractory
patients who have had a 4- to 6-week trial at 20 mg/day.
Generalized Anxiety Disorder:
Same as for depression
Elderly:
5-10 mg per day. Treatment refractory patients may
require 20 mg/day after a trial of 4-6 weeks on 10 mg/day.
III. Half-Life: 30 hr.
A. Clinical Guidelines:
Compared to the SSRIs, escitalopram
has low overall effects on P450 enzymes (see table 2).
Compared to the racemate (citalopram), escitalopram has an
improved side-effect profile.
B. Drug Interactions:
Cytochrome P450: Modest inhibition of
the hepatic enzyme, CYP2D6, may lead to mild elevations of
TCAs and antiarrhythmics (see Tables 1 & 2). This interaction
is unlikely to be clinically significant.
Fluoxetine (Prozac, Sarafem, Prozac
Weekly)
I. Indications:
Effective for depressive and anxiety disorders.
Preparations:
10, 20 mg capsules; 20 mg/5 mL solution; 10 mg
scored tablet; 90 mg weekly tablet.
II. Dosage:
A. Depression:
20 mg qAM is usually effective. May increase to
maximum dose of 80 mg/day. Increase dose by 20 mg/day
each month in partial responders. Most patients respond at a
dosage between 20-40 mg/day.
B. Obsessive-Compulsive Disorder (OCD):
20 mg/day.
Increase by 20 mg/day each month if needed. Treatment of
OCD may require a higher dosage than depression. Maxi-
mum dose of 80 mg/day.
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