General side
effects are mostly present during the first 1-4 weeks while the body adapts to the drug (with the exception of sexual side effects,
which tend to occur later in treatment). In fact, it often takes 6-8 weeks for the drug to begin reaching its full potential (the
slow onset is considered a downside to treatment with SSRIs). Almost all SSRIs are known to cause one or more of these symptoms:
anhedonia
apathy
nausea/vomiting
drowsiness
or somnolence
headache
bruxism (clenching of teeth)
extremely vivid and strange dreams
dizziness
fatigue
mydriasis (pupil dilation)
urinary
retention
changes in appetite
changes in sleep
weight loss/gain (measured by a change in bodyweight of 7 pounds)
may result in a double
risk of bone fractures and injuries
changes in sexual behaviour (see the next section)
increased feelings of depression and anxiety
(which may sometimes provoke panic attacks)
tremors
autonomic dysfunction including orthostatic hypotension, increased or reduced sweating
akathisia
liver
or renal impairment
suicidal ideation (thoughts of suicide)
photosensitivity (increased risk of sunburn) (use protective clothing and
sunscreen to decrease the risk of sunburn.)
mania or hypomania (users with some type of bipolar disorder are at a much higher risk)
Many side effects disappear after the adaptation phase, when the antidepressant effects begin to come to prominence. However,
despite being called general, the side effects and their durations are highly individual and drug-specific. Usually the treatment
is begun with a small dose to see how the patient's body reacts to the drug, after that either the dose can be adjusted (eg. Prozac
in the UK is begun at a 20 mg dose, and then adjusted as necessary to 40 mg or 60 mg). Should the drug prove not to be effective,
or the side effects intolerable to the patient, another common route is to switch treatment to either another SSRI, or an SNRI (Serotonin-norepinephrine
reuptake inhibitor).
Sexual side effects
SSRIs can cause various types of sexual dysfunction such as anorgasmia, erectile dysfunction,
and diminished libido. Initial studies found that such side effects occur in less than 10% of patients, but since these studies relied
on unprompted reporting, the frequency was probably underestimated. In more recent studies, doctors have specifically asked about
sexual difficulties, and found that they are present in between 17% and 41% of patients.
On the other hand, the effect of SSRIs to
slow down sexual stimulation may be used as treatment; SSRIs have been proposed as a drug to treat premature ejaculation.
Cardiovascular
side effects
Cardiovascular side effects are very rare with SSRI use, with a reported incidence of less than 0.0003 percent. SSRIs
inhibit cardiac and vascular sodium, calcium and potassium channels and prolong QT intervals. However, a number of large studies of
patients without known pre-existing heart disease have reported no EKG changes related to SSRI use. In overdose, fluoxetine has been
reported to cause sinus tachycardia, myocardial infarction, junctional rhythms and trigeminy. Some authors have suggested electrocardiographic
monitoring in patients with severe pre-existing cardiovascular disease who are taking SSRI's.
Post-SSRI sexual dysfunction
According
to one source, Post-SSRI sexual dysfunction (PSSD) is an iatrogenic type of sexual dysfunction caused directly by the previous use
of SSRI antidepressants. While apparently uncommon, it can last for months, years, or sometimes indefinitely after the discontinuation
of SSRIs.
Suicidality and aggression
Similarly to other antidepressants, SSRIs can cause suicidality in children. Analyses of
the risks of SSRIs by governing bodies in the United States and United Kingdom have produced warnings about suicidality and aggression
when the medications are used with children and adolescents.
In some countries SSRIs have a black box warning regarding the first few
weeks of use recommending hypervigilance on the part of family and friends when an SSRI is first prescribed. There has been campaigning
for this black box warning to be implemented in the UK, as it has been recommended since 2004, but has not yet been introduced.
SSRIs
and pregnancy
The U.S. Food and Drug Administration issued a warning on July 19, 2006 stating nursing mothers on SSRIs must discuss
treatment with their physicians.
When taken by pregnant women, selective serotonin reuptake inhibitors (SSRIs) cross the placenta and
have the potential to affect newborns.
Neonatal abstinence syndrome
Neonatal abstinence syndrome is a withdrawal syndrome in
newborn babies. It has been documented in SSRI treatment. By November 2003, a total of 93 cases of SSRI use associated with either
neonatal convulsions or withdrawal syndrome had been reported. Subsequently, the authors of a Lancet study concluded that doctors
should avoid or cautiously manage the prescribing of these drugs to pregnant women with psychiatric disorders.
Persistent pulmonary
hypertension
Persistent pulmonary hypertension (PPHN) is a serious and life-threatening, but rare, lung condition that occurs soon
after birth of the newborn. Newborn babies with PPHN have high pressure in their lung blood vessels and are not able to get enough
oxygen into their bloodstream. About 1 to 2 babies per 1000 babies born in the U.S. develop PPHN shortly after birth, and often they
need intensive medical care. One study has found that PPHN is six times more common in babies whose mothers take an SSRI antidepressant
after the 20th week of the pregnancy compared to babies whose mothers do not take an antidepressant.
Withdrawal
SSRI discontinuation
syndrome, also known as SSRI withdrawal syndrome or SSRI cessation syndrome, is a withdrawal syndrome that can occur during or following
the interruption, lowering of dose or discontinuation of regular SSRI or SNRI antidepressant drug usage. The condition often begins
between 24 hours to one week after reduction in dosage or complete discontinuation, depending on the elimination half-life of the
drug. The prescribing labels of SSRIs acknowledge the possibility of "intolerable" discontinuation reactions, and some patients have
extreme difficulty discontinuing use from SSRI drugs.
SSRIs are not addictive in the conventional medical use of the word (i.e. animals
given free access to the drug do not actively seek it out and do not seek to increase the dose), but discontinuing their use can produce
both somatic and psychological symptoms.
"Brain zaps" and "electric shock sensations"
Symptoms described as "brain zaps", "brain
shocks," "brain shivers" or "head shocks" are a withdrawal symptom experienced during discontinuation (or reduction of dose) of antidepressant
drugs. The symptoms are widely variable in description and of unknown medical origin; common descriptions include dizziness, electric
shock-like sensations, sweating, nausea, insomnia, tremor, confusion, and vertigo. The MedDRA "preferred term" for coding these types
of symptoms in adverse drug reaction reports (for use in pharmacovigilance databases such as under the Yellow Card Scheme), is paraesthesia.
In
a 1997 survey, a "sizable minority" of medical professionals were not confidently aware of the existence of antidepressant withdrawal
symptoms. A 2005 review of adverse event reporting showed that descriptions of "electric shocks" from patients on paroxetine had been
reported more frequently than some other symptoms.
Prevention and treatment
Patients should be advised of the elimination
half-life times on their specific medication, and patients should be aware if changing from a long half-life medication, to a shorter
one, that taking their dose regularly becomes much more important. Patients taking SSRIs with longer halflifes can often miss several
doses without noticing any discomfort, but the shorter halflife of other SSRIs means that a single missed dose may cause withdrawal
symptoms (e.g. paroxetine).
The condition may be avoided by either recommencing the original, and/or lesser dose of the SSRI (or a
similar SSRI), or slowly reducing the dosage over several weeks or months. While slowly reducing the dosage does not guarantee that
a patient will not experience the discontinuation syndrome, it is considered a safer method than abrupt discontinuation. Gradual discontinuation,
or tapering, or titration, can be accomplished by breaking pills into parts or using a graduated oral syringe with the liquid form.
Using the liquid form of any of the drugs is always more helpful for withdrawal.
Treatment is dependent on the severity of the discontinuation
reaction and whether or not further antidepressant treatment is warranted.
Contraindications and Interactions
One
major contraindication of SSRIs is the accompanying use of MAOIs (monoamine oxidase inhibitors). This is likely to cause severe serotonin
syndrome, and could result in death.
People taking SSRIs should also avoid taking pimozide (an antipsychotic diphenylbutylpiperidine
derivative). The atypical opioid analgesic tramadol hydrochloride (or Ultram, Ultracet) can, in rare cases, produce seizures when
taken in conjunction with an SSRI or tricyclic antidepressant. Liver impairment is another contraindication for medications of this
type.
SSRIs may increase blood levels and risk of toxicities of certain medications:
highly protein-bound medications like warfarin
(coumadin) and digoxin
antiarrhythmic agents like propafenone (Rythmol) or flecainide (Tambocor)
beta blockers like metoprolol (Toprol
xl) or propranolol (Inderal)
tricyclic antidepressants like amitriptyline (Elavil) (may increase risk of serotonin syndrome)
benzodiazepines
like alprazolam (Xanax) or diazepam (Valium)
carbamazepine (Tegretol)
cisapride (Propulsid)
clozapine (Clozaril)
ciclosporin (Neoral)
haloperidol
(Haldol)
phenytoin (Dilantin)
pimozide (Orap)
theophylline (Theo-dur)
Certain drugs may increase toxicities of SSRIs:
alcohol and
other CNS depressants
diuretics (water pills)
MAOIs
sympathomimetic drugs like pseudoephedrine (Sudafed)
lithium
sibutramine (Meridia)
MDMA
(ecstasy)
zolpidem (ambien)
Dextromethorphan
tramadol (synergistic serotoninergic effect said to increase risk of seizure)
Pethadine is
also reported as causing dangerous interactions
