Medications · Mood and anxiety · Uncategorized

When depression meds don’t work: antidepressant amplifiers

Sometimes depression doesn’t get better, not with a single antidepressant. With all the medications on the market and all the pressure not to prescribe, what should a psychiatrist do?  Add more medication, and the patient has side effects.  Withhold medications, and they suffer or worse.  People are complicated.  Medications are complicated.  But then there are augmenters, and they always bring hope.

To clarify: this article is about medications that jumpstart antidepressants.

Imagine a 23-year old woman sitting before you, bright, an incredible future ahead of her, if only she can shake her misery.  Physically, she has no energy, she sleeps too much, and her body feels so heavy at times she can hardly move.  The woman complains of hopelessness, helplessness, and amidst all that her thoughts are awry.  She struggles to find words and can’t seem to make decisions. 

You’re thinking, is this really depression?  It’s the right question.  You never want to miss a neurological disease in hiding or some hormonal thyroid problem.  Anything.  But we’ve got the diagnosis right.  This is depression.

You’re thinking, is there some stressor driving it?  Has she tried therapy?  That’s also a good question.  The psychiatrist has talked to her extensively.  The woman describes average stress, nothing major, nothing to explain the depth of her despair.  She describes it as a feeling, not a thought.  Of course there could be some hidden but profound memory that’s driving the depression.  Just to make sure, the psychiatrist refers her to a therapist.  Six months later, the patient is still in misery.

You’re thinking, it’s time for medication.  A good conclusion.  Severe depression almost always requires medication.  The psychiatrist starts her on an antidepressant, advances it to the highest dose, and the woman responds… partially.  She’s slightly better, she reports, but still depressed.  There’s a sense of relief.  Bringing that depression down a few notches is better than nothing.

But what next?

Pause a moment.  Doctors have a special little book.  It’s small enough to fit into the pocket, carries a worn plasticized cover, and the print is very small.  That’s where we carry all our treatment algorithms.  An algorithm is a little equation.  You drop in information, and the equation pumps out solutions.  The algorithm for helping someone with a partial response to a medication gives you three options:

  • Switch the antidepressant to something else
  • Add a second antidepressant
  • Add an “augmenting agent” to help jumpstart the first antidepressant.

As mentioned, this article is about the third option.  An augmenting agent is a supplemental or add-on medication that helps get the first medication going.  Here’s a partial list of augmenting agents for antidepressants in depression.  

Thyroid hormone.  Thyroid hormone as an augmenting agent is one of the oldest tricks in the book.  Doctors have been jumpstarting antidepressants this way for decades.   How did this start?  People with too little thyroid hormone in their body have a tendency to feel depressed.  They are mentally and physically slowed.  Somewhere way back a psychiatrist started thinking.  A bit of experimentation did it.  Turns out thyroid hormone can relieve mental and physical slowing in depressed people without thyroid problems.  Side effects include anxiety, loss of appetite, dizziness, and sensitivity to heat.  Chest pain and osteoporosis are rare.

Lithium.  Lithium has been around for more than fifty years.  It was noticed early on to be effective for depression.  Typically used in bipolar disorder, Lithium exhibits an anti-depressant effect even in people who don’t have bipolar disorder.  The dose used for normal depression is typically much lower than used in people with bipolar disorder.  Side effects can include weight gain, shakes, problems during pregnancy, acne, diarrhea, thirst, excessive urination, and rarely thyroid and kidney problems.

Lamotrigine, or Lamictal.  Like Lithium, Lamictal is often used for bipolar depression.  However, it has been shown to help depressed people without bipolar disorder, especially those with mood swings.  The most concerning side effect is a rare, life-threatening rash.  Start this medication at a low dose and increase it very slowly reduces the risk of this rash.

Atypical antipsychotics (AAP).  AAP’s can be helpful for depression.  Examples include Quetiapine (Seroquel), Aripiprazole (Abilify), and Risperidone (Risperdal).  To a degree these medications are antidepressants in their own right but not strong enough to be used alone.  They’re especially helpful when depression is accompanied by agitation, confused thinking, racing thoughts, insomnia, or hallucinations.  Side effects can include sleepiness or insomnia, weight gain, sugar or cholesterol problems, movement problems, and very seizures, heart problems, or coma.  Atypical antipsychotics should be used with care in patients with dementia.

Stimulants. Stimulants include amphetamines as well as wakefulness-promoting medications like Modafinil (Provigil) or caffeine.  Stimulants are especially helpful in patients who sleep too much, have little energy, and exhibit slowed thinking/concentration problems.  They should be avoided in people with anxiety or heart problems. Side effects include high blood pressure, fast heart rate, weight loss, anxiety, fidgetiness, jerking movements, and poor sleep.  Amphetamines are addicting.  These medications are usually avoided in patients with substance abuse issues.

Benzodiazepines (BZ).  BZ’s are helpful for anxious depression or when a person struggles with insomnia.  Examples include Lorazepam (Ativan) and Clonazepam (Klonopin).  Side effects include sedation, loss of impulse control, and at high doses, breathing problems and coma.  These medications can be very addictive, so doctors try to avoid using them in people with substance abuse problems.  Usually BZ’s are used on a short-term basis.

Over-the-counter (OTC) augmentation strategies.  The major concern with OTC treatments include medication interactions and potential to worsen physical problems.  Some work directly on mood (SAM-E, 5-HTP, Omega-3 Fatty Acids).  Others target sleep or pain.


Here’s a recap.  In case you’re struggling with difficult-to-treat depression, here’s the psychiatrist’s typical approach:

1- Make sure they have all the right psychiatric diagnoses (like childhood trauma, substance abuse, personality disorder)

2- Make sure they’re not missing something medical (pancreatic cancer, hypothyroidism)

3 – Trial of talk-therapy (cognitive behavioral therapy, dialectical behavioral therapy, etc)

4 – Trial of mainstream medication at maximum doses over adequate time period

5 – Switch meds, add a second antidepressant, or go for the augmentation approach

If you haven’t responded to medications, remember there are other options.   There are always options.   They include:

6 – A trial of monoamine oxidase inhibitors (MAOI)

7 – Electroconvulsive therapy

8 – Transcranial magnetic stimulation

9 – Ketamine infusion therapy

10 – Vagus nerve stimulation

11 – Hospitalization.  Expert polypharmacy (combining medications)

 

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