HAM side effects

(antiHistamine—sedation, weight gain;

antiAdrenergic—hypotension;
antiMuscarinic (anticholinergic)—dry mouth, blurred
vision, urinary retention, constipation, exacerbation of neurocognitive
disorders (i.e., dementias).
 Found in tricyclic antidepressants (TCAs) and low-potency anti psychotics.

Serotonin syndrome: Confusion, flushing, diaphoresis, tremor,

myoclonic jerks, hyperthermia, hypertonicity, rhabdomyolysis, renal
failure,and death.
■ Occurs when there is too much serotonin, classically when :
 Selective serotonin reuptake inhibitors (SSRIs) and monoamine
oxidase inhibitors (MAOIs) are combined.
 As this combination is rarely seen in practice anymore, serotonin
syndrome is more commonly seen when a patient is prescribed
multiple medications with serotonergic activity (e.g.,
SSRIs/SNRIs, trazodone, Tramadol, triptans, dextromethorphan,
St. John’s wort, ondansetron).
■ Treatment: Stop medications, supportive care.

Hypertensive crisis: Caused by a buildup of stored catecholamines;

triggered by the combination of MAOIs with tyramine-rich foods (e.g.,
red wine, cheese, chicken liver, cured meats) or with sympathomimetics.

Extrapyramidal side effects (EPS):

3Parkinsonism—
masklike face,
cog wheel rigidity,
bradykinesia,
pill-rolling tremor;
akathisia—restlessness,need to move, and agitation;
dystonia—sustained, painful contraction of muscles of neck, tongue,
eyes, diaphragm.
■ Occur more frequently with high-potency, typical (first generation)
antipsychotics, but can also be seen with atypical (second generation)
antipsychotics.
■ Reversible.
■ Occur within hours to days of starting medications or increasing doses.
■ In rare cases, can be life threatening (e.g., dystonia of the diaphragm
causing asphyxiation).

 Hyperprolactinemia:
 Occurs with high-potency, typical (first generation) antipsychotics
and risperidone.

Tardive dyskinesia (TD): Choreoathetoid muscle movements, usually of

the mouth and tongue (can affect extremities, as well).
■ Occurs after years of antipsychotic use (more likely with high-potency,
first-generation antipsychotics).
■ Usually irreversible.

Neuroleptic malignant syndrome: Mental status changes, fever,

tachycardia, hypertension, tremor, elevated creatine phosphokinase
(CPK), “lead pipe” rigidity.
■ Can be caused by any antipsychotic after a short or long time
(increased with high-potency, typical antipsychotics).
■ A medical emergency with up to a 20% mortality rate.

Drug interactions: Cytochrome P450 is a group of enzymes in the liver

that metabolizes many common drugs, including psychiatric medications.
■ Some medications induce the system, in other words the system
metabolizes medications faster—drug levels decrease.
■ Some medications inhibit the system, in other words the system
metabolizes medications more slowly—drug levels increase.
■ Common cytochrome P450 enzymes important in metabolizing
psychiatric medications include CYP3A4, CYP2D6, CYP1A2, CYP2C9,
CYP2C19.

Important CYP450 inducers include:

■ Tobacco (1A2).
■ Carbamazepine (1A2, 2C9, 3A4).
■ Barbiturates (2C9).
■ St. John’s wort (2C19, 3A4).
■ Important CYP450 inhibitors include:
■ Fluvoxamine (1A2, 2C19, 3A4).
■ Fluoxetine (2C19, 2C9, 2D6).
■ Paroxetine (2D6).
■ Duloxetine (2D6).
■ Sertraline (2D6).

Antidepressants
The major categories of antidepressants are:
■SSRIs.
■ SNRIs.
■ Heterocyclic antidepressants, including TCAs and tetracyclic

antidepressants.
■ MAOIs.

■ Miscellaneous antidepressants
All antidepressants have similar response rates in treating major depression
but differ in safety and side-effect profiles.
■ Approximately 60 to 70% of patients with major depression will respond

to an antidepressant medication.
■ It usually takes 4 to 6 weeks on a given dose of an antidepressant for a

patient to fully benefit from a trial of the medication.

■ For patients who are prone to side effects, it’s important to start at a low

dose and titrate up slowly.

■ Many antidepressants have a withdrawal phenomenon, characterized by

Dizziness
, headaches
, nausea,
insomnia,
and malaise;
depending on the dose and half-life, they may need to be tapered.
■ Because of their safety and tolerability, SSRIs and related antidepressants

have become the most common agents used to treat major depression.
However,
++ the choice of a particular medication used for a given patient
should be made based on:
■ Patient’s particular symptoms

■ Previous treatment responses by the patient or a family member to a

particular medication
■ Side-effect profile

■ Comorbid (medical and psychiatric) conditions

■ Risk of suicide via overdose on the medication

■ Cost

__

Antidepressant Use in Other Disorders

■ OCD(Obsessive-compulsive disorder ): SSRIs (in high doses), TCAs (clomipramine).
■ Panic disorder: SSRIs, SNRIs, TCAs, MAOIs.
■ Eating disorders: SSRIs (in high doses), TCAs.

■ Persistent depressive disorder (dysthymia): SSRIs, SNRIs (e.g., venlafax

ine, duloxetine).
■ Social anxiety disorder (social phobia): SSRIs, SNRIs, MAOIs.

■ GAD: SSRIs, SNRIs (venlafaxine), TCAs.

■ Posttraumatic stress disorder: SSRIs.

■ Irritable bowel syndrome: SSRIs, TCAs.

■ Enuresis: TCAs (imipramine).

■ Neuropathic pain: TCAs (amitriptyline and nortriptyline), SNRIs.

■ Chronic pain: SNRIs, TCAs.
■ Fibromyalgia: SNRIs.
■ Migraine headaches: TCAs (amitriptyline).

■ Smoking cessation: Bupropion.

■ Premenstrual dysphoric disorder: SSRIs.

■ Insomnia: Mirtazapine, trazodone, TCAs (doxepin).

SELECTIVE SEROTONIN REUPTAKE INHIBITORS

■ mechanism of action :SSRIs inhibit presynaptic serotonin pumps that
take up serotonin, leading to increased availability of serotonin in
synaptic clefts. Additionally, SSRIs cause downstream effects increasing
brain plasticity—this mechanism has been hypothesized to explain the
delay to onset of antidepressant effect.
+ ‫الزبده يعمل تثبيط للمبمب الي تأخذ السيروتين بالتالي حيزيد عدد السيرتونين المتوفر للعمل‬
‫نقطة الدون ستتريم ايفيكت هوا المسل عن اللونق افيكت اوف الميديكيشن‬
■ Although structural differences are minimal, patients often respond
differently (in regards to efficacy and side effects) to different SSRIs.
■ Based on their half-lives, most SSRIs can be dosed daily. Fluoxetine
has a weekly dosing form available, as well There is no correlation
between plasma levels and efficacy or side effects.
■ SSRIs are the most commonly prescribed antidepressants due to several
distinct advantages:
■ Low incidence of side effects, most of which resolve with time.
■ No food restrictions.
■ Much safer in overdose.
■ Examples of SSRIs include:
■ Fluoxetine (Prozac):
 ■ Longest half-life, with active metabolites; therefore, no need to
taper.
 ■ Safe in pregnancy, approved for use in children and
adolescents.
 ■ Common side effects: insomnia, anxiety, sexual dysfunction.
 ■ Can elevate levels of antipsychotics, leading to increased side
effects.
■ Sertraline (Zoloft):
 ■ Higher risk for gastrointestinal (GI) disturbances.
 ■ Very few drug interactions.
 ■ Other common side effects: insomnia, anxiety, sexual
dysfunction.
■ Paroxetine (Paxil):
 ■ A potent inhibitor of CYP26, which can lead to several drug–
drug interactions.
  ■ Common side effects: anticholinergic effects (e.g., sedation,
constipation, weight gain) and sexual dysfunction.
 ■ Short half-life leading to withdrawal phenomena if not taken
consistently.
■ Fluvoxamine (Luvox):
■ Currently approved only for use in obsessive-compulsive disorder
(OCD).
■ Common side effects: nausea and vomiting.
■ Multiple drug interactions due to CYP inhibition.
■ Citalopram (Celexa):
■ Fewest drug–drug interactions.
■ Dose-dependent QTc prolongation.
■ Escitalopram (Lexapro):
■ Levo-enantiomer of citalopram; similar efficacy, possibly fewer side
effects.
■ Dose-dependent QTc prolongation.
Side Effects
■ SSRIs have significantly fewer side effects than TCAs and MAOIs due
to serotonin selectivity (they do not act on histamine, adrenergic, or
muscarinic receptors).
■ They are much safer in overdose. Most side effects occur because of
the extensive number of serotonin receptors throughout the body,
including the GI tract.
■ Many of the side effects of SSRIs resolve within a few days to weeks
and include:
■ GI disturbance: Mostly nausea and diarrhea; giving with food can help.
■ Insomnia; also vivid dreams, often resolves over time.
■ Headache.
■ Weight changes (up or down).
■ Other side effects include:
■ Sexual dysfunction (30–40%): decreased libido, anorgasmia, delayed
ejaculation. These may occur weeks to months after taking an SSRI and
typically do not resolve.
■ Restlessness: An akathisia-like state.
Serotonin syndrome: Caused by an excess of serotonin in the body.
It can result from taking a single serotonergic agent, or by taking multiple
serotonergic agents in combination.
One example is triptans (for migraine headaches) used with SSRIs.
Serotonin syndrome is characterized
by fever,
diaphoresis,
tachycardia,
hypertension,
delirium, and
neuromuscular excitability (especially hyperreflexia and “electric jolt”
limb movements),
potentially death.
■ Hyponatremia: Rare.
■ Seizures: Rate of approximately 0.2%, slightly lower than TCAs.

SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS ( S N R

Is )
■ Venlafaxine (Effexor):
■ Often used for depressive disorders, anxiety disorders like generalized
anxiety disorder (GAD), and neuropathic pain.
■ Low drug interaction potential.
■ Extended release (XR form) allows for once-daily dosing.
■ Side-effect profile similar to SSRIs, with the exception of increased
blood pressure (BP) in higher doses; do not use in patients with
untreated or labile BP.
■ New form, desvenlafaxine (Pristiq), is the active metabolite of
venlafaxine;it is expensive and without known benefit over venlafaxine.
■ Duloxetine (Cymbalta):
■ Often used for people with depression, neuropathic pain, and in
fibromyalgia.
■ Side effects are similar to SSRIs, but more dry mouth and constipation
relating to its norepinephrine effects.
■ Hepatotoxicity may be more likely in patients with liver disease or
heavy alcohol use, so liver function tests should be monitored when
indicated
MISCELLANEOUS ANTIDEPRESSANTS
■ Bupropion (Wellbutrin):
■ Norepinephrine-dopamine reuptake inhibitor.
■ Relative lack of sexual side effects as compared to the SSRIs.

■ Some efficacy in treatment of adult attention deficit hyperactivity disorder

(ADHD)
■ Effective for smoking cessation.

■ Weight neutral.

■ Side effects include increased anxiety, as well as increased risk of seizures

and psychosis at high doses.

■ Contraindicated in patients with epilepsy or active eating disorders,

and in those currently on an MAOI. Use with caution with agents that
also lower the seizure threshold (like stimulants).
Serotonin Receptor Antagonists and Agonists
■ Trazodone (Desyrel) and Nefazodone (Serzone):

■ Useful in the treatment of major depression, major depression with

anxiety, and insomnia (secondary to its sedative effects).

■ They do not have the sexual side effects of SSRIs and do not affect

rapid eye movement (REM) sleep.

■ Side effects include nausea, dizziness, orthostatic hypotension, cardiac

arrhythmias, sedation, and priapism (especially with trazodone).

■ Because of orthostatic hypotension in higher doses, trazodone is not

frequently used solely as an antidepressant. It is commonly used to treat insomnia often when
initiating an SSRI (until insomnia improves
as the depression resolves).
■ Nefazodone carries a Black Box Warning for rare but serious liver

failure (1 per 250,000–300,000 people) and is rarely used.

α2-Adrenergic Receptor Antagonists
■ Mirtazapine (Remeron):

■ Useful in the treatment of major depression, especially in patients

who have significant weight loss and/or insomnia.

■ Side effects include sedation, weight gain, dizziness, tremor, dry

mouth, constipation, and (rarely) agranulocytosis.

■ Fewer sexual side effects compared to SSRIs and few drug interactions