Sertraline is an antidepressant in the SSRI class.
It was one of the first SSRIs to enter the market and it remains a very popular psychiatric
medication.
Along with being used for depression, it is also used for OCD, anxiety, and other conditions.
As always, there will be more information and links to references on TheDrugClassroom.com
which you can find using the link below.
The primary positive effects include depression reduction, mood improvement, and anxiety reduction.
Among the potential negatives are nausea, headache, diarrhea, sexual dysfunction, insomnia,
dry mouth, drowsiness, dizziness, tremor, and fatigue.
Efficacy has been demonstrated in depression, dysthymia, OCD, social anxiety, panic disorder,
PTSD, premature ejaculation, and premenstrual dysphoric disorder.
It's also sometimes used in eating disorders.
As with other psychiatric medications, Sertraline isn't going to be effective for everyone.
It has a similar efficacy to other SSRIs, SNRIs, and TCAs in the treatment of depression.
There are some trends in favor of its efficacy relative to other common antidepressants,
so it may be a good first-line treatment.
It's specifically used as a first-line treatment in cases of depression where someone has cardiovascular
disease.
Although it does work in the long-term for many people, the greatest evidence of efficacy
is seen over a period of months.
It appears relapse rates increase over time.
Even if treatment is continued in someone who has responded to the drug, it might not
permanently keep major depression from returning.
For minors, the primary indication is in OCD, where it has been shown to be effective.
It might be effective in other disorders like depression and anxiety.
Sertraline can be ineffective and potentially negative for depression and anxiety symptoms
when treatment first begins.
Some benefit is often noticed after the first week, and the efficacy builds over the following
3 to 8 weeks.
The primary negatives in medical settings are sexual dysfunction, drowsiness, dizziness,
headache, increased sweating, dry mouth, agitation, and insomnia.
Sexual dysfunction is one of the main complaints with Sertraline and other SSRIs.
Patients may experience decreased libido, anorgasmia, delayed ejaculation, and decreased
pleasure.
Sexual dysfunction appears to be less significant with sertraline compared to paroxetine, citalopram,
and venlafaxine.
Though it's higher than with mirtazapine.
For other negatives, it may cause less constipation, fatigue, and weight gain than paroxetine.
While the incidence of diarrhea is greater.
Sertraline is an isomer of a Tametraline derivative.
It primarily functions as a serotonin reuptake inhibitor.
Some minor dopamine reuptake inhibition does exist and is of unclear clinical relevance.
How SSRIs provide their beneficial effects still isn't understood.
It's currently believed the effects come from something more complex than the drug's initial
serotonin uptake inhibition.
There's an immediate impact on serotonin activity, yet it can take 4 weeks or more for the full
benefits to emerge.
I'll briefly discuss a few possibilities, but it should be noted that more research
is definitely needed.
An overarching view is that adaptations in the brain are responsible.
This could mean desensitization of 5-HT1A auto-receptors, which could facilitate greater
serotonin activity.
BDNF could also be playing a role as it's associated with neuronal outgrowth, repair,
and other important activities.
BDNF seems to increase with Sertraline and lower basal levels of BDNF can be seen in
depression.
Along with raising BDNF, there are other possible factors that contribute to the support and
growth of neurons and synapses.
As such, the drug might be providing its benefit at least partly through neurogenesis.
There's a high serotonin hypothesis that's based around depression actually being an
energetically expensive state associated with higher serotonin activity.
This model suggests initial SSRI effects are neutral or negative, but prolonged use can
actually provide benefits by altering serotonergic activity and reducing glutamatergic activity.
Another way of looking at the effects involves an impact of SSRI's on low-level information
processing.
There's evidence that they could move the processing towards positive versus negative
associations.
This kind of impact on processing enables a re-learning process that can take weeks
to become clearly beneficial.
In 1977, Kenneth Koe, a chemist in the Pfizer Pharmacology Department, was looking at stuctural
features of potent and relatively selective uptake inhibitors.
He worked with another Pfizer employee, Willard Welch, to have a set of Tametraline derivatives
synthesized.
Those derivatives were tested and Sertraline was picked out of the group due to its selective
and potent nature.
The drug was patented in 1979.
In vitro and in vivo studies were carried out in the 1980s.
They showed Sertraline was an effective serotonin uptake blocker in rats.
The tests also confirmed it was quite selective for serotonin.
Studies in humans found it was well-tolerated even up to 400 mg and exhibited fewer side
effects than TCAs.
It was approved in the UK in 1990.
The FDA approved Sertraline under the name Zoloft in 1991, and it was officially launched
in February 1992.
Between the 1990s and 2000s, the drug was investigated and adopted for many uses.
Early in its history, it was being used alongside just a few other SSRIs:
Fluoxetine, Paroxetine, and Fluvoxamine.
Many health professionals were largely unaware of some of the problematic aspects of SSRIs,
particularly their withdrawal effects.
This meant patients were also often unaware of exactly how Sertraline could impact their
lives both on and off the drug.
Knowledge about the withdrawal effects has grown over time, but adequate info still may
not be provided to patients.
Around 2005, the drug was generating revenue of $2 to $3 billion annually.
In 2013, it was most the popular antidepressant in the US and the second biggest psychiatric
medication.
There were about 40 million prescriptions.
The drug is usually started at 25 to 50 mg per day.
From there, dose adjustments can be made based on treatment response, generally ending with
a maintenance dose of 50 to 200 mg per day.
Sertraline is unscheduled in the US, though it's a prescription-only substance.
It's often a prescription-only drug in other countries.
Sertraline has historically been viewed as largely safe in orverdose.
Some of the symptoms include drowsiness, tachycardia, tremor, nausea, and vomiting.
Even up to a few thousand milligrams has been largely non-problematic.
While it's possible to have a severely dangerous response just from Sertraline, most deaths
involve combinations.
In medical settings, most of the severe adverse effects are rare.
There are some reports of abnormal bleeding, tremor, and syncope.
Sertraline may also increase panic attacks and anxiety in some people, though this could
be followed by a therapeutic anxiolytic effect.
When there are negative effects, they're more along the lines of nausea, insomnia, sweating,
and sexual dysfunction.
There are some potential liver health concerns for a very small group of patients.
It normally has no or very minimal effect on the liver, but a few reports exist of hepatotoxicity.
In general, if you have any significant negative effects, you should notify your prescribing
physician.
Serotonin syndrome is one of the concerns with Sertraline.
Although it could potentially occur with Sertraline itself (generally with a very large overdose),
it's most often a concern when another serotonergic drug is used.
This means, for example, that it should not be used with MAOIs.
Serotonin syndrome can be deadly, but most cases treated at a medical center resolve
in 24 hours.
Withdrawal does exist with Sertraline.
It doesn't occur for everyone, but a significant portion do experience some form of withdrawal.
Usually the symptoms appear within a few days of stopping or reducing your dose and they're
relatively mild.
They then resolve between 1 day and a few weeks after the onset.
A common duration of symptoms is around 5 to 8 days.
Some of the effects include flu-like symptoms, insomnia, decreased concentration, irritability,
headache, dizziness, and nausea.
Another issue is electric shock sensations that very in intensity.
They can sometimes impair normal functioning, such as by affecting walking and driving.
Those sensations don't occur in all patients.
Prolonged symptoms lasting more than 6 weeks are rare, but they've occasionally been reported.
Those include disturbed mood, depression, mood swings, irritability, insomnia, anxiety,
impaired concentration, and impaired memory.
These issues can be distinct from the patient's original condition.
It's not understood why the majority of people experience temporary symptoms, while some
people report prolonged issues lasting months or years.
Tapering is recommended.
A lot of people still report symptoms after they fully end their use, but tapering is
a good strategy to potentially reduce the severity of symptoms.
Greater risk of suicidal thoughts and behavior is one of the potential concerns with SSRIs
that has received a lot of attention.
Most of the data suggests there's a very low risk of suicidal activity, but that doesn't
mean it never occurs.
A sudden onset of aggression and suicidal ideation is possible.
If you have symptoms of that sort or know someone who does, the physician should be
contacted.
Monitoring a patient is especially important during the first 1 to 2 months.
There's some evidence that the risk varies by age.
The suicide risk may be unaffected or lower over the age of 24, while it could be unaffected
or slightly higher for younger people.
The risk may also vary to some extent between antidepressants, with Sertraline generally
considered low-risk.
Some of the risky combinations include MAOIs, Dextromethorphan, and Tramadol.