Pregnancy

• Risk Category C [some animal studies show adverse effects; no controlled studies in humans]

• Not generally recommended for use during pregnancy, especially during first trimester

• Should evaluate patient for treatment with an antidepressant with a better risk/benefit ratio

Breast Feeding

• Some drug is found in mother’s breast milk

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Should evaluate patient for treatment with an antidepressant with a better risk/benefit ratio

SELEGILINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Treatment-resistant depression

• Patients with atypical depression (hypersomnia, hyperphagia)

• Patients who wish to avoid weight gain and sexual dysfunction

• Parkinson’s patients inadequately responsive to levodopa

Potential Disadvantages

• Noncompliant patients

• Patients with motor complications and fluctuations on levodopa treatment

• Patients with cardiac problems or hypertension

Primary Target Symptoms

• Depressed mood (depression)

• Somatic symptoms (depression)

• Sleep and eating disturbances (depression)

• Psychomotor disturbances (depression)

• Motor symptoms (Parkinson’s disease)

Pearls

• Transdermal administration may allow freedom from dietary restrictions

• Transdermal selegiline theoretically appealing as a triple action agent (serotonin, norepinephrine, and dopamine) for treatment-refractory and difficult cases of depression

• Transdermal selegiline may have low risk of weight gain and sexual dysfunction, and may be useful for cognitive dysfunction in attention deficit disorder and other cognitive disorders, as it increases dopamine and is metabolized to l-amphetamine and l-methamphetamine

• Low-dose oral administration generally used as an adjunctive treatment for Parkinson’s disease after other drugs have lost efficacy

• At oral doses used for Parkinson’s disease, virtually no risk of interactions with food

• Neuroprotective effects are possible but unproved

✽ Enhancement of levodopa action can occur for Parkinson’s patients at low oral doses, but antidepressant actions probably require high oral doses that do not have the potential tissue selectivity and lack of dietary restrictions of the low-dose transdermal formulation

✽ High doses may lose safety features

• MAOIs are generally reserved for second-line use after SSRIs, SNRIs, and combinations of newer antidepressants have failed

• Patient should be advised not to take any prescription or over-the-counter drugs without consulting their doctor because of possible drug interactions

• Headache is often the first symptom of hypertensive crisis

• Myths about the danger of dietary tyramine can be exaggerated, but prohibitions against concomitant drugs often not followed closely enough

✽ Combining multiple psychotropic agents with MAOIs should be for the expert, especially if combining with agents of potential risk (e.g., stimulants, trazodone, TCAs)

✽ MAOIs should not be neglected as therapeutic agents for the treatment-resistant

Table 1. Drugs contraindicated due to risk of serotonin syndrome/toxicity

Do Not Use:
Antidepressants	Drugs of Abuse	Opioids	Other
SSRIs	MDMA (ecstasy)	Meperidine	Non-subcutaneous sumatriptan
SNRIs	Cocaine	Tramadol	Chlorpheniramine
Clomipramine	Methamphetamine	Methadone	Brompheniramine
St. John’s wort	High-dose or injected amphetamine	Fentanyl	Dextromethorphan
			Procarbazine?

Table 2. Dietary guidelines for patients taking MAOIs

Foods to avoid*	Foods allowed
Dried, aged, smoked, fermented, spoiled, or improperly stored meat, poultry, and fish	Fresh or processed meat, poultry, and fish; properly stored pickled or smoked fish
Broad bean pods	All other vegetables
Aged cheeses	Processed cheese slices, cottage cheese, ricotta cheese, yogurt, cream cheese
Tap and unpasteurized beer	Canned or bottled beer and alcohol
Marmite	Brewer’s and baker’s yeast
Sauerkraut, kimchee
Soy products/tofu	Peanuts
Banana peel	Bananas, avocados, raspberries
Tyramine-containing nutritional supplement

* Not necessary for 6-mg transdermal or low-dose oral selegiline

Table 3. Drugs that boost norepinephrine: should only be used with caution with MAOIs

Use With Caution:
Decongestants	Stimulants	Antidepressants with norepinephrine reuptake inhibition	Other
Phenylephrine	Amphetamines	Most tricyclics	Phentermine
Pseudoephedrine	Methylphenidate	NRIs	Local anesthetics containing vasoconstrictors
	Cocaine	NDRIs
	Methamphetamine
	Modafinil		Tapentadol
	Armodafinil

Suggested Reading

Bodkin JA, Amsterdam JD. Transdermal selegiline in major depression: a double-blind, placebo-controlled, parallel-group study in outpatients. Am J Psychiatry 2002;159(11):1869–75.

Kennedy SH. Continuation and maintenance treatments in major depression: the neglected role of monoamine oxidase inhibitors. J Psychiatry Neurosci 1997;22:127–31.

Shulman KI, Walker SE. A reevaluation of dietary restrictions for irreversible monoamine oxidase inhibitors. Psychiatr Ann 2001;31:378–84.

SERTINDOLE

SERTINDOLE: THERAPEUTICS

Brands

• SERDOLECT

see index for additional brand names

Generic?

No

Class

• Atypical antipsychotic (serotonin-dopamine antagonist; second generation antipsychotics; also a mood stabilizer)

Commonly Prescribed for

(bold for FDA approved)

• Schizophrenia (for patients intolerant to at least one other antipsychotic)

• Acute mania/mixed mania

• Other psychotic disorders

• Bipolar maintenance

• Bipolar depression

• Treatment-resistant depression

How the Drug Works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis and stabilizing affective symptoms

• Blocks serotonin 2A receptors, causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms

✽ Serotonin 2C properties may contribute to antidepressant actions

How Long Until It Works

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior as well as on cognition

• Classically recommended to wait at least 4–6 weeks to determine efficacy of drug, but in practice some patients may require up to 16–20 weeks to show a good response, especially on cognitive symptoms

If It Works

• Most often reduces positive symptoms but does not eliminate them

• Can improve negative symptoms, as well as aggressive, cognitive, and affective symptoms in schizophrenia

• Most schizophrenia patients do not have a total remission of symptoms but rather a reduction of symptoms by about a third

• Perhaps 5–15% of schizophrenia patients can experience an overall improvement of greater than 50–60%, especially when receiving stable treatment for more than a year

• Such patients are considered super-responders or “awakeners” since they may be well enough to be employed, live independently, and sustain long-term relationships

• Continue treatment until reaching a plateau of improvement

• After reaching a satisfactory plateau, continue treatment for at least a year after first episode of psychosis

• For second and subsequent episodes of psychosis, treatment may need to be indefinite

• Even for first episodes of psychosis, it may be preferable to continue treatment