Psych Pharmacy: Depression Treatment and Overview

Psych Pharmacy: Depression Treatment and Overview

Editor's Note: It is with great pleasure that I introduce Nina Vadiei, PharmD. Nina is a totally bad ass PGY2 Psych Pharmacy Resident who has written the excellent post you're about to read. She's sort of like a wizard when it comes to all things 'psych,' and we really appreciate her dropping knowledge bombs here for you all.

Pro Tip: There is a whole bunch of awesome dosing charts at the end of this post. 

Take it away, Nina!

 

Psychiatry and Voodoo Medicine

Hi everyone. I’m not going to lie, when I was first asked to make a review about psychiatric medicine for tl;dr pharmacy, I was skeptical at whether or not I could contribute in a conversational and fun way. Because let’s face it, a lot of people think psych is the worst.

Most people's reaction to psych pharmacy (Image)

Most people's reaction to psych pharmacy (Image)

But, I was very recently inspired by someone who referred to the field of psychiatry as “voodoo medicine.”

You see, psych was my first-love. Some people empathize more with cancer patients, with the critically ill, or maybe those with diabetes. For me, I feel the most strongly for patients who feel they can’t control the negative feelings impacting their lives... 

Hearing demons telling them to kill themselves... 

And being called crazy... 

When really they have a disorder they can’t control causing them to go without sleep for days at a time and to talk unnaturally fast.

In this past week alone, I’ve had patients come through the psych emergency department saying they wanted to shoot 20 people (uh, we’ve had enough mass public shootings happen lately, #amirite).

So yeah, I empathize not only for those suffering from mental illness themselves, but also for the lives impacted by mental illness indirectly.

Most people hear mental health and automatically think of depression or psychosis. For the former, a chunk of the population thinks of people who whine about feeling low, and are not trying hard enough to just be happy. For the latter, people imagine what you might see in an insane asylum like in American Horror Story. Where people are hospitalized after cutting off the head of their sister's dog (yes, I also encountered this story recently).

I understand being horrified at these stories. And I get that you can be annoyed by the "bratty" teenage girl/boy claiming they want to kill themselves because they can’t take it anymore.

But, similar to how I believe beauty is in the eye of the beholder, I believe that our perception of things is what shapes our reality. Try using your empathy skills to get into the patient's shoes. 

Don't look at a depressed person and say "You're not trying hard enough." Instead try to imagine feeling down for no reason whatsoever. For days or weeks on end. And having everyone around you tell you that "You’re in control of your own happiness." But of course you're not able to control it no matter how hard you try.

Would that make you feel worse, or better about yourself?

Imagine it being like an illness that's outside of your control. Like cancer. Or if you’re diagnosed with "stupidly high" cholesterol despite exercising and eating a balanced diet, because it runs in your family (yes, this actually happens).

It’s no different with depression. We all have different brain chemistries. And some of us are genetically predisposed to mental disorders. Just like people are predisposed to high cholesterol, diabetes, autoimmune disorders, cancers, you name it.

Just because someone tells you can overcome high cholesterol and diabetes with exercise and healthy eating alone, does that mean you shouldn't seek extra help through medications? Especially if lifestyle changes alone didn't work?

NO. DERP.

And clearly, even though this disgusting shaming of people who take psych medicines exists....the bottom line is, people want to live life to the fullest. And medicine CAN help us live better lives. Please, do some research before you just repeat something you heard from Facebook about how bad medications are.

So again, I get that my colleague, a very intelligent pharmacist, would refer to psych as "voodoo medicine."

Not only is mental health constantly referred to as something that can simply be overcome if you "choose" to, it is an area of medicine that has a lot of advancing to do. Studying how the brain functions and how medication affects those processes, is extremely difficult. And it's got to be researched very differently than say, the impact of Lipitor on reducing the frequency of cardiovascular events.

A lot of the research depends on interviewing patients to assess for medication response, which in itself is a whole other skill that has to be learned aside from diagnosing/prescribing medicine. There's not a simple "LDL" marker that can be objectively measured.

The fact is, psychiatry is an art AND a science. It’s an art in that it takes knowing what questions to ask, and how to talk to people to be able to effectively treat them. It’s a science in that it still requires knowing, based on a patients subjective reporting of their symptoms:

  • What their diagnosis is
  • What this means in terms of where the chemical imbalance lies
  • And choosing the optimal medication to correct that (which means taking into consideration interacting medicines they’re already taking, substances the patient may be abusing that may interact, cost, patient preference and tolerability, medical co-morbidities that may affect how well the medication works or exacerbate side effects, etc).

This is no easy task. It usually takes more than one trial of medication to figure out what will help someone and cause the least amount of side effects.

But just because it takes more than one try, does not make this “voodoo medicine.”

People think that if a medication does not IMMEDIATELY work (because pills are supposed to be MAGICAL, DUH!) that it has failed.

We wish our pills were this magical (Image)

We wish our pills were this magical (Image)

I too wish that all medicine could work right away. Maybe one day it will (probably not, calm down). But for now, give things time to work. The #1 reason medicines fail people in psychiatry is noncompliance (meaning people stop taking the medicine because they think it’s not working or don’t want to deal with the side-effects).

You have to give the medicine time to work (which takes usually more than a month in psych, given you have to get to the right dose for each individual person). 

Are you better yet? Now? How about now? (Image)

Are you better yet? Now? How about now? (Image)

And you have to find the medicine that won’t cause side-effects (which also varies between individual people).

But I’ll go ahead and end my “Why psychiatry is not voodoo medicine” rant here.

Continue on to learn about the pharmacology (whether it’s just to brush up on psych knowledge for the NAPLEX or because you’re a super-star pharmacist). You’ll better understand why this is all true.

I'll also provide a whole bunch of super handy dosing charts if you make it all the way to the bottom ;)

 

Depression 

Here's what most people think depression is:


Feeling down, hopeless, and even suicidal (boohoo, get out more, go exercise, stop beating yourself up so much, get out there and meet someone!)
 

Here's what depression really is:

  1. Five or more of the following symptoms present nearly every day for at least a two week period with symptoms resulting in a change in function (at least one must be depressed mood OR loss of interest or pleasure)
  • Depressed mood most of the time on most days (feeling sad, empty, appearing tearful)
  • Decreased interest or pleasure in daily activities most of the time on most days (can be self-reported or noted by others)
  • Significant changes in weight (more than 5% weight change in a month)
  • Significant changes in sleep; hypersomnia or insomnia
  • Psychomotor agitation or retardation (self-reported or observed)
  • Fatigue or decreased energy
  • Feelings of worthlessness or inappropriate guilt
  • Decreased concentration of difficult making decisions
  • Recurrent thoughts of death, suicidal ideation (SI)

In addition, symptoms have to result in "significant distress" or impair daily function. As in you have a hard time getting out of bed and going to work because you don't see the point. Also, the symptoms cannot be secondary to substance abuse or to a general medical condition (such as hypothyroidism). This actually happens a lot!

Yeah, it’s not as easy as “get out of that funk, man!” If your daily function is impaired, or you’re so distressed you can’t even get out of bed, it’s just not that simple.

I once had a 72 year old female patient who was so severely depressed she began to hear voices. It got so bad that she became catatonic and unable to communicate (this can. seriously. happen.) We could tell because she kept covering her ears during the interview, and couldn’t stop crying. The only word she muttered in a 30-minute intake was “Help.”

Yeah, please. Tell that helpless old lady to just "get over it."

Ok. Let's assume I've convinced you that some people with depression need medication. How do you choose what to use?

  • Patient preference
  • Prior response
  • Safety
  • Tolerability and adverse effects
  • Co-morbid disorders
  • Potential drug-drug interactions
  • Pharmacokinetic parameters
  • Cost

Wait. That looks sort of like the run down for how to treat every disease state. Maybe that's a little too obvious for you?

Okay, here’s what the treatment guidelines say.

 

1.       First-line:

  • Psychotherapy +/- SSRI (selective serotonin reuptake inhibitor), SNRI (selective norepinephrine reuptake inhibitor), mirtazapine, bupropion
  • If the patient also has psychotic features, use an antidepressant + antipsychotic
  • Electroconvulsive therapy (ECT) for severe depression

2.       Second-line:

  • Switch to different medication from list above (first-line) as monotherapy
  • Augment with antidepressant with different mechanism
  • Augment with atypical antipsychotic
  • Augment with psychotherapy (if not already)

As you can see, there are many, many options!

3.       Third-line:

  • Switch to medication with different mechanism from list above
  • Augment with different antidepressant with different mechanism or a Tricyclic Antidepressant (TCA)
  • Augment with lithium

4.       Treatment resistance:

  • ECT
  • Monoamine Oxidase Inhibitor (MAOI)

 

If you’re like me, you read that first-line list and thought “but which SSRI or SNRI?” or “How do I choose between all those?” That’s where the list above the guidelines comes into play. Here are some examples/rules of thumb.

  • If someone is having a lot of trouble sleeping and decreased appetite, choose an agent that is more sedating and increases appetite such as mirtazapine
  • If someone is elderly, choose something with more evidence for safety in the elderly population, such as escitalopram or sertraline (for SSRIs), or mirtazapine, bupropion, and venlafaxine (due to less anticholinergic side-effects)
  • If someone is on other QTc prolonging meds, or has cardiovascular co-morbidities, avoid agents that can further prolong the QTc, such as citalopram
  • If someone is having more GI side-effects (nausea/vomiting/diarrhea), avoid agents that contribute to GI side effects, such as sertraline
  • If someone is having a lot of anxiety, avoid medications that tend to cause more anxiety side-effects (though all anti-depressants can increase anxiety within the initial 1-2 weeks), such as sertraline or fluoxetine

Overall, common side-effects of SSRIs are: nausea/vomiting (this makes sense, because we use serotonin antagonists to treat and prevent nausea/vomiting), effects on sleep (SSRIs can increase somnolence or insomnia...so it can really go in either direction), CNS side-effects (dizziness, headache), and sexual dysfunction (decreased interest, inability to orgasm or have an erection), and increased anxiety (initially).

Often times, side-effects go away after a few weeks of being on the medication, but most patients don’t want to wait for bad things to resolve on their own, as I’ve mentioned previously.

You should also warn people of the BLACK BOX WARNING that comes with all antidepressants of increased suicidality risk in children, adolescents, and young adults 24 and younger...

…BUT, what if the medication is working really well for the depression but is giving the patient nausea!? Or tired?!

You don’t have to change the med! Tell them to take it at bedtime, problem solved (genius, right?!)

What if they have insomnia?!
Take it in the morning (brilliant, I know. I can do this all day.)

What about the sexual dysfunction?
Yeah, that sucks. Try a different one. Bupropion is often a good choice for those who've experienced sexual side effects. 

That brings up another good point. What if you need to switch someone to a different antidepressant?

You can’t just take them off of it, right?

Or they might relapse and become worse/suicidal?

Can’t people become tolerant to antidepressants and need more or another?

  1. Yes.
  2. No.
  3. NoOoOoO…

Chill.

Except this guy. He likes feeling crappy. Image

Except this guy. He likes feeling crappy. Image

Yeah, if they’ve been taking an antidepressant for over a month, especially one that’s short-acting (see tables below), you should slowly taper that person off before switching to prevent what’s called discontinuation syndrome.

This does not mean going off medicine abruptly will cause someone to become suicidal or go bonkers. They will just feel crappy, and no one likes feeling crappy! These are symptoms they may experience:

  • Anxiety
  • Irritability
  • Sadness
  • Insomnia
  • Headache
  • Nausea
  • Electric shock sensations

In all of these cases, the highest risk is with agents that have a short half-life. Paroxetine has the shortest half life, so that would be the worst offender here. The lowest risk would be with fluoxetine.  

These are basically…the basics... regarding the approach to take for treating depression!

Congrats for making it through all that (if you’re still reading this).

As a special prize for making it this far, I will now reward you with some fun magical kinetics/dosing tables to refer to (because who the hell can memorize all this?). I'll also give you some useful tidbits on some of the "other" depression drugs we haven't talked about yet. You're welcome.

KINETICS:

Drug (SSRIs) Half-life Active Metabolite CYP Enzyme
Citalopram 35 h No 3A4, 2C19, 2D6
Escitalopram 27-32 h No 3A4, 2C19
Fluoxetine 4-6 days Yes 2C9, 2D6
Paroxetine 24 h No 2D6
Sertraline 26 h Yes 2C9, 2C19, 2D6, 3A4

Drug (SNRIs) Half-Life Active Metabolite CYP Enzyme
Desvenlafaxine 10-11 h No 3A4 (minor)
Duloxetine 12 h No 1A2, 2D6
Venlafaxine 5 h Yes 2D6

Bupropion: Tmax occurs in 2-5 hours (IR vs. XL); Metabolized by CYP 2D6
Mirtazapine: T½ 37 h in females (PAH, female power!), 26 h in males; Metabolized by CYP2D6, CYP1A2, CYP3A4

DOSING:

Drug (SSRIs) Initial Range Renal Adjust Hepatic Adjust
Citalopram 20 mg 20-40 mg None Max 20 mg
Escitalopram 10 mg 10-20 mg None Max 10 mg
Fluoxetine 20 mg 20-80 mg None None
Paroxetine 20 mg 10-50 mg Max 40 mg Max 40 mg
Sertraline 50 mg 50-200 mg None None

Drug (SNRIs) Initial* Range* Renal Adjust Hepatic Adjust
Desvenlafaxine 50 mg 50-100 mg CrCl 30-50: Max 50 mg
CrCl <30: Max 50 mg QoD
None
Duloxetine 60 mg 60 mg CrCl <30: Do not use Do not use
Venlafaxine 37.5-75 mg 75-375 mg (IR)
75-225 mg (XR)
Mild-mod impairment: Decrease 25-50%
Dialysis: Decrease 50%
Decrease by 50% or more
*mg/day

Bupropion:
  1. IR: Initial 100 mg BID (range 300-450 mg/day)
  2. SR: Initial 150 mg qAM (range 300-400 mg/day…divided)
  3. XL: 150 mg qAM (range 150-300 mg/day…once daily)

Mirtazapine:
  1. Initial 15 mg at bedtime, range 15-45 mg at bedtime
  2. Lower doses (not higher) are more sedating (more histamine activity)

SPECIAL POPULATION CONSIDERATIONS: (we’re all special in our own ways… ಠ‿ಠ)

Drug (SSRIs) Pregnancy Lactation Elderly Pediatrics
Citalopram C Not recommended Max 20 mg/day Safety/efficacy not established
Escitalopram C Not recommended Max 10 mg/day 10-20 mg/day in 12 and older
Fluoxetine C Not recommended Lower initial dose 10-20 mg/day in 8 and older
Paroxetine D* Undetectable in breast milk Max 40 mg/day Safety/efficacy not established
Sertraline C Undetectable in breast milk No adjustment needed No approved dosing
*septal wall defects

Drug (SNRIs) Pregnancy Lactation Elderly Pediatrics
Desvenlafaxine C Not recommended No adjustment Safety/efficacy not established
Duloxetine C Not recommended No adjustment Safety/efficacy not established
Venlafaxine C Not recommended No adjustment Safety/efficacy not established

 

Other Drugs Used for Depression

And here's some additional pointers for some of the non-SSRI/SNRI drugs used in depression...

Bupropion:

  • Pregnancy category C
  • Not recommended in breast-feeding due to lack of data
  • Pediatric safety/efficacy not established
  • Elderly requires reduced frequency and/or daily dose
  • Renal impairment requires reduced frequency and/or daily dose
  • Hepatic impairment (mild-moderate, reduce frequency and/or daily dose) (severe; maximum dose is 75 mg)
  • Do not use in those with history of seizure disorder or with eating disorders (bupropion can significantly lower the seizure threshold) 

Mirtazapine:

  • Pregnancy category C
  • Not recommended in breast-feeding due to lack of data
  • Pediatric safety/efficacy not established
  • Elderly require slower dose increased due to less clearance
  • Renal impairment, same as above
  • Hepatic impairment, same as above

If you want information on tricyclic antidepressants (TCAs) or the monoamine oxidase inhibitors (MAOIs)…
Too bad, they suck; you most likely shouldn’t be using them.

j/k. (Kind of).

Here’s a brief summary just for you.

Tricyclic Antidepressants (TCAs):

  • amitriptyline
  • doxepin
  • nortriptyline
  • desipramine
  • clomipramine

Adverse effects:

They're sedating. They have loads of anticholinergic effects (blurred vision, urinary retention, dry mouth, constipation, cognitive impairment/delirium). They cause orthostatic hypotension.

But the main concern with TCAs is the potential for fatal overdose (via cardiac toxicity through v-tach or heart block). This is the main "thing" that put TCAs out of favor. Cardiac toxicity is very rare with SSRIs/SNRIs.

Monoamine Oxidase Inhibitors (MAOIs):

  • phenelzine
  • isocarboxazid
  • selegiline

Adverse effects:

Nothing too major. Just a little thing called hypertensive crisis (which is exactly what it sounds like). NBD, right? Of course, they can also cause headache, anticholinergic effects, hypotension, bradycardia, edema (use a slow titration to avoid this), and sexual dysfunction. 

Sign me up, right?!

On top of all of that, they interact with basically every drug under the sun. Serotonergic agents are contraindicated because there is an additive risk of serotonin syndrome. And then sympathomimetic agents are also contraindicated because of the hypertensive crisis thing.

Got a stuffy nose? NO SUDAFED FOR YOU!

But wait, there's more!

You have to moderate (and possibly eliminate) foods that contain tyramine. Monamine Oxidase happens to break down tyramine into serotonin...so if you had a bunch more serotonin (through tyramine) you get that lovely serotonin syndrome/hypertensive crisis thing.

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